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1.
Eur J Sport Sci ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978338

RESUMO

Pregnancy and childbirth involve substantial physical, physiological and psychological changes. As such, postpartum rugby players should be supported and appropriately prepared to return to the demands of rugby alongside the additional demands of motherhood. This review aims to discuss specific perinatal considerations that inform a rugby player's readiness to return-to-sport postpartum and present an approach to rehabilitation. Before engaging in full rugby training and matchplay, postpartum players should have progressed through the initial phases of rehabilitation and graded sports-specific training to prepare them for the loads they will be exposed to. Additional rehabilitation considerations include minimising deconditioning during pregnancy; medical concerns; the abdominal wall; the pelvic floor; perinatal breast changes, breastfeeding and risk of contact breast injury; body mass; nutritional requirements; hormonal considerations; athlete identity and psychological considerations; joining team training; return to contact and tackle training; evaluating player load tolerance and future research, policy and surveillance needs. A whole-systems, biopsychosocial approach following an evidence informed return-to-sport framework is recommended when rehabilitating postpartum rugby players. Health and exercise professionals are encouraged to use the perinatal-specific recommendations in this review to guide the development of postpartum rehabilitation protocols and resources.

3.
Int J Gynecol Cancer ; 34(7): 1051-1059, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950927

RESUMO

OBJECTIVES: To develop a pre-operative tool to estimate the risk of peri-operative packed red blood cell transfusion in primary debulking surgery. METHODS: We retrospectively reviewed an institutional database to identify patients who underwent primary debulking surgery for ovarian cancer at a single center between January 1, 2001 and May 31, 2019. Receiver operating characteristic curve and area under the receiver operating characteristic curve (AUC) were calculated. Five-fold cross-validation was applied to the multivariate model. Significant variables were assigned a 'BLOODS' (BLood transfusion Over an Ovarian cancer Debulking Surgery) score of +1 if present. A total BLOODS score was calculated for each patient, and the odds of receiving a transfusion was determined for each score. RESULTS: Overall, 1566 patients met eligibility criteria; 800 (51%) underwent a peri-operative blood transfusion. Odds ratios (OR) were statistically significant for American Society of Anesthesiologists scores of 3 and 4 (OR 1.34, 95% confidence interval (95% CI) 1.09 to 1.63), pre-operative levels of cancer antigen 125 (CA125) (OR 2.43, 95% CI 1.98 to 2.99), platelets (OR 1.59, 95% CI 1.45 to 1.74), obesity (OR 0.76, 95% CI 0.60 to 0.96), presence of carcinomatosis (OR 2.45, 95% CI 1.93 to 3.11), bulky upper abdominal disease (OR 2.86, 95% CI 2.32 to 3.54), pre-operative serum albumin level (OR 0.31, 95% CI 0.24 to 0.40), and pre-operative hemoglobin level (OR 0.56, 95% CI 0.51 to 0.61). The corrected AUC was 0.748 (95% CI 0.693 to 0.804). BLOODS scores of 0 and 5 corresponded to 11% and 73% odds, respectively, of receiving a peri-operative blood transfusion. CONCLUSIONS: We developed a universal pre-operative scoring system, the BLOODS score, to help identify patients with ovarian cancer who would benefit from surgical planning and blood-saving techniques. The BLOODS score was directly proportional to the American Society of Anesthesiologists score, presence of upper abdominal disease, carcinomatosis, CA125 level, and platelets level. We believe this model can help physicians with surgical planning and can benefit patient outcomes.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos de Citorredução/métodos , Idoso , Transfusão de Sangue/estatística & dados numéricos , Transfusão de Sangue/métodos , Medição de Risco/métodos , Adulto
4.
J Am Chem Soc ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023430

RESUMO

Photoactivatable or "caged" pharmacological agents combine the high spatiotemporal specificity of light application with the molecular specificity of drugs. A key factor in all optopharmacology experiments is the mechanism of uncaging, which dictates the photochemical quantum yield and determines the byproducts produced by the light-driven chemical reaction. In previous work, we demonstrated that coumarin-based photolabile groups could be used to cage tertiary amine drugs as quaternary ammonium salts. Although stable, water-soluble, and useful for experiments in brain tissue, these first-generation compounds exhibit relatively low uncaging quantum yield (Φu < 1%) and release the toxic byproduct formaldehyde upon photolysis. Here, we elucidate the photochemical mechanisms of coumarin-caged tertiary amines and then optimize the major pathway using chemical modification. We discovered that the combination of 3,3-dicarboxyazetidine and bromine substituents shift the mechanism of release to heterolysis, eliminating the formaldehyde byproduct and giving photolabile tertiary amine drugs with Φu > 20%─a 35-fold increase in uncaging efficiency. This new "ABC" cage allows synthesis of improved photoactivatable derivatives of escitalopram and nicotine along with a novel caged agonist of the oxytocin receptor.

5.
Front Vet Sci ; 11: 1348084, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962706

RESUMO

A newborn female, Holstein calf weighing approximately 38.5 kg developed severe, persistent colic caused by a large colostrum curd located within the calf's abomasum. Based upon 10% body weight, the calf had been fed 4 liters (L) of first-milking colostrum approximately 30 min after birth and an additional 2 L of first-milking colostrum 6 h after the first feeding. Both the first and second feedings used an esophageal tube feeder to deliver the colostrum. Colic developed shortly after the second colostrum feeding. The affected calf did not respond to on-farm supportive medical therapy and was humanely euthanized by a penetrating captive bolt approximately 22 h after the onset of colic. This on-farm colostrum feeding protocol is routinely observed in the current dairy industry. This case demonstrates calves that are fed large volumes of colostrum during a relatively short window of time may develop a large, firm colostrum curd within the abomasum that causes abdominal distension, colic, and occasional death. There is an urgent need for prospective analytical studies that determine the optimal immunoglobulin mass (g/L) and the ideal volume of colostrum fed to newborn calves for both the first and second colostrum feedings within the most beneficial time frame. Guidelines should be developed that minimize complications that adversely affect calf health and well-being while ensuring the successful transfer of passive immunity.

6.
Sci Rep ; 14(1): 15140, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956234

RESUMO

Rapamycin slows cystogenesis in murine models of polycystic kidney disease (PKD) but failed in clinical trials, potentially due to insufficient drug dosing. To improve drug efficiency without increasing dose, kidney-specific drug delivery may be used. Mesoscale nanoparticles (MNP) selectively target the proximal tubules in rodents. We explored whether MNPs can target cystic kidney tubules and whether rapamycin-encapsulated-MNPs (RapaMNPs) can slow cyst growth in Pkd1 knockout (KO) mice. MNP was intravenously administered in adult Pkd1KO mice. Serum and organs were harvested after 8, 24, 48 or 72 h to measure MNP localization, mTOR levels, and rapamycin concentration. Pkd1KO mice were then injected bi-weekly for 6 weeks with RapaMNP, rapamycin, or vehicle to determine drug efficacy on kidney cyst growth. Single MNP injections lead to kidney-preferential accumulation over other organs, specifically in tubules and cysts. Likewise, one RapaMNP injection resulted in higher drug delivery to the kidney compared to the liver, and displayed sustained mTOR inhibition. Bi-weekly injections with RapaMNP, rapamycin or vehicle for 6 weeks resulted in inconsistent mTOR inhibition and little change in cyst index, however. MNPs serve as an effective short-term, kidney-specific delivery system, but long-term RapaMNP failed to slow cyst progression in Pkd1KO mice.


Assuntos
Modelos Animais de Doenças , Camundongos Knockout , Nanopartículas , Doenças Renais Policísticas , Sirolimo , Animais , Sirolimo/administração & dosagem , Sirolimo/farmacologia , Camundongos , Doenças Renais Policísticas/tratamento farmacológico , Doenças Renais Policísticas/metabolismo , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/patologia , Nanopartículas/administração & dosagem , Serina-Treonina Quinases TOR/metabolismo , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo , Rim/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Sistemas de Liberação de Medicamentos , Masculino
7.
MedEdPORTAL ; 20: 11410, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957533

RESUMO

Introduction: For future success in the modern health care environment, health professions students require effective interprofessional education experiences to develop their perceptions of other professionals on the health care team. The Interprofessional Standardized Patient Experience (ISPE) is an interprofessional education activity for prelicensure health professional students in nursing, pharmacy, physical therapy, medicine, social work, and occupational therapy. Methods: The ISPE involved collaboration among students to conduct a subjective interview. Students from six health care professions individually interviewed a simulated patient while being observed by students from other professions. A structured faculty-guided debriefing session followed the comprehensive interview process. Students completed a voluntary pre- and post-ISPE survey with interprofessional questions and feedback on the activity. Descriptive statistics were used to analyze individual responses. Differences in student opinions by student profession and by the number of professions present were examined using chi-square tests. Results: Over 4 consecutive academic years, 1,265 students completed the ISPE, and 1,028 completed the pre- and post-ISPE surveys. Analysis of the survey responses indicated that the ISPE enhanced student awareness of the functions of an interprofessional team and increased student knowledge of the roles of different health care professions. Students rated the ISPE as a valuable experience. Differences were noted in some of the measures by profession and group size. Discussion: A single ISPE had a significant impact on prelicensure students' perceptions. The ISPE is a novel and effective approach to interprofessional education that students appreciate.


Assuntos
Educação Interprofissional , Relações Interprofissionais , Estudantes de Ciências da Saúde , Humanos , Educação Interprofissional/métodos , Inquéritos e Questionários , Estudantes de Ciências da Saúde/psicologia , Simulação de Paciente , Equipe de Assistência ao Paciente , Comportamento Cooperativo , Masculino , Ocupações em Saúde/educação
8.
Sci Transl Med ; 16(754): eadi6887, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959328

RESUMO

Virulent infectious agents such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and methicillin-resistant Staphylococcus aureus (MRSA) induce tissue damage that recruits neutrophils, monocyte, and macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes, and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2-infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage, and cytokine storm. These results demonstrate essential roles for PI3Kγ in inflammatory lung disease and support the potential use of PI3Kγ inhibitors to suppress inflammation in severe infectious diseases.


Assuntos
COVID-19 , Classe Ib de Fosfatidilinositol 3-Quinase , Inflamação , SARS-CoV-2 , COVID-19/patologia , Classe Ib de Fosfatidilinositol 3-Quinase/metabolismo , Animais , Inflamação/patologia , Humanos , Tratamento Farmacológico da COVID-19 , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Pulmão/patologia , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Síndrome da Liberação de Citocina/tratamento farmacológico , Permeabilidade Capilar/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/patologia
9.
Comput Inform Nurs ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963331

RESUMO

Nurses and clinicians require knowledge and training of their facilities' code blue response cart to manage emergency scenarios. However, the nurses who access the carts change frequently through turnover and role changes. An augmented reality training solution was built for mobile devices, but encountered distribution and access challenges. This study evaluated the conversion of the mobile application to a desktop-based version deployed via a learning management system. Eight hundred fifty clinicians were assigned the interactive learning product, which collected anonymous usage data and an optional feedback survey within the module. Of 850 assigned users, 468 completed the module, and 338 completed the feedback survey. Respondents indicated a positive difference of 25.3% in retrospective pre/post confidence and an appreciation for the features of the product. Performance measured by decreasing total item search time appeared to level off after three plays. The format transition was successful, allowing the same widespread distribution as the mobile versions of [X]. Feedback gathered will drive improvements in the module.

10.
Neuro Oncol ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38982561

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-ß). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-ß-mediated immune suppression in the TME. METHODS: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-ß, which programs tumor-specific T cells to convert TGF-ß from an immunosuppressant to an immunostimulant. Bispecific IL-13Rα2/TGF-ß CAR-T cells were evaluated for efficacy and safety against both patient-derived GBM xenografts and syngeneic models of murine glioma. RESULTS: Treatment with IL-13Rα2/TGF-ß CAR-T cells leads to greater T-cell infiltration and reduced suppressive myeloid cell presence in the tumor-bearing brain compared to treatment with conventional IL-13Rα2 CAR-T cells, resulting in improved survival in both patient-derived GBM xenografts and syngeneic models of murine glioma. CONCLUSION: Our findings demonstrate that by reprogramming tumor-specific T-cell responses to TGF-ß, bispecific IL-13Rα2/TGF-ß CAR-T cells resist and remodel the immunosuppressive TME to drive potent anti-tumor responses in GBM.

11.
Behav Brain Res ; 472: 115146, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39009189

RESUMO

Mental imagery may represent a weaker form of perception and, thus, mental images may be more ambiguous than visual percepts. If correct, the acquisition of fear would be less specific for imagined fears in comparison to perceptual fears, perhaps facilitating broader fear generalization. To test this idea, a two-day differential fear conditioning experiment (N = 98) was conducted. On day one, two groups of participants underwent differential fear conditioning such that a specific Gabor patch orientation (CS+) was paired with mild shocks (US) while a second Gabor patch of orthogonal orientation (CS-) was never paired with shock. Critically, one group imagined the Gabor patches and the other group was visually presented the Gabor patches. Next, both groups were presented visual Gabor patches of similar orientations (GCS) to the CS+. On day two, to assess the persistence of imagined fear, participants returned to the lab and were tested on the GCS devoid of shock. For day one, in contrast to our primary hypothesis, both self-report and skin conductance response measures did not show a significant interaction between the GCS and groups. On day two, both measures demonstrated a persistence of imagined fear, without US delivery. Taken together, rather than demonstrating an overgeneralization effect, the results from this study suggest that imagery-based fear conditioning generalizes to a similar extent as perceptually acquired fear conditioning. Further, the persistence of imagery-based fear may have unique extinction qualities in comparison to perceptual-based fear.

12.
Int J Geriatr Psychiatry ; 39(7): e6123, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39019648

RESUMO

OBJECTIVES: Sensory impairment is a hypothesized risk factor for cognitive decline; however, the psychosocial pathways are not well understood. We evaluated whether the association between visual impairment (VI) and cognitive decline was partially mediated via depressive symptoms, loneliness, or social activity. METHODS: We used data from 2601 older adults enrolled in the Memory and Aging Project in 1997 and the Minority Aging Research Study in 2004 with neuropsychological tests across five domains measured annually for up to 16 years. VI was assessed with the Rosenbaum Pocket Vision Screener. Depressive symptoms, loneliness, and social activity were self-reported using validated scales. We used structural equation models to estimate the associations of VI with baseline and change in cognitive function, directly and indirectly through each mediator (depressive symptoms, loneliness, and social activity). We evaluated mediation via "psychological distress" using a latent variable combining depressive symptoms and loneliness. RESULTS: The association between VI and global cognitive decline was mediated via lower social activity (indirect effect) [95% confidence interval (CI)] of linear slope: -0.025 (-0.048, -0.011), via loneliness (-0.011 [95% CI: -0.028, -0.002]), and via psychological distress (-0.017 [95% CI: -0.042, -0.003]). We did not find sufficient evidence for mediation via depressive symptoms alone. CONCLUSIONS: The harmful effect of VI on cognitive decline may be partially mediated through loneliness and lower social activity.


Assuntos
Disfunção Cognitiva , Solidão , Transtornos da Visão , Humanos , Solidão/psicologia , Feminino , Masculino , Idoso , Disfunção Cognitiva/psicologia , Idoso de 80 Anos ou mais , Transtornos da Visão/psicologia , Depressão/psicologia , Testes Neuropsicológicos , Fatores de Risco , Pessoa de Meia-Idade , Participação Social/psicologia
13.
Int J Prison Health (2024) ; 20(2): 156-171, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38984605

RESUMO

PURPOSE: Women are exposed to vulnerabilities that can lead to drug use or hinder recovery. However, there is a dearth of studies on recovery programs for women. This study aims to add to the literature by examining the feasibility of a women-only aftercare program for recovering users in the Philippines. DESIGN/METHODOLOGY/APPROACH: The study used a mixed-method design with pre and post-program surveys used to measure changes in participants' recovery capital. Focused group discussions elicited participants' context, their reactions, perceived outcomes and suggestions on the program. FINDINGS: Women in the program shared narratives of pain, trauma and abuse before treatment. Participants reported significant improvements in personal, community and family recovery capital dimensions. The program enabled personal growth in the form of new knowledge, skills and self-confidence. The women-only program also provided a safe space for women, to receive support from other women, community members and family. However, the women continue to face continuing challenges related to stigma and discrimination and a lack of livelihood opportunities. RESEARCH LIMITATIONS/IMPLICATIONS: A limitation of the study was its small sample size and the lack of a control group. Another limitation was the variability in treatment received by the women, which could have affected overall outcomes. Future studies using a randomized control trial and longitudinal designs may provide more robust conclusions on the effectiveness of the program. PRACTICAL IMPLICATIONS: Given punitive contexts, gender-sensitive and trauma-informed programs and services for women involved in drug use could potentially mitigate the abuse, stigma and vulnerabilities they experience. ORIGINALITY/VALUE: This study contributes to the sparse literature on women-only aftercare, particularly in countries that criminalize drug use.


Assuntos
Assistência ao Convalescente , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Filipinas , Adulto , Assistência ao Convalescente/métodos , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Pessoa de Meia-Idade , Grupos Focais , Estigma Social
14.
mSphere ; : e0036024, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980072

RESUMO

Characterizing microbial communities at high resolution and with absolute quantification is crucial to unravel the complexity and diversity of microbial ecosystems. This can be achieved with PCR assays, which enable highly selective detection and absolute quantification of microbial DNA. However, a major challenge that has hindered PCR applications in microbiome research is the design of highly specific primer sets that exclusively amplify intended targets. Here, we introduce Phylogenetically Unique Primers in python (PUPpy), a fully automated pipeline to design microbe- and group-specific primers within a given microbial community. PUPpy can be executed from a user-friendly graphical user interface, or two simple terminal commands, and it only requires coding sequence files of the community members as input. PUPpy-designed primers enable the detection of individual microbes and quantification of absolute microbial abundance in defined communities below the strain level. We experimentally evaluated the performance of PUPpy-designed primers using two bacterial communities as benchmarks. Each community comprises 10 members, exhibiting a range of genetic similarities that spanned from different phyla to substrains. PUPpy-designed primers also enable the detection of groups of bacteria in an undefined community, such as the detection of a gut bacterial family in a complex stool microbiota sample. Taxon-specific primers designed with PUPpy showed 100% specificity to their intended targets, without unintended amplification, in each community tested. Lastly, we show the absolute quantification of microbial abundance using PUPpy-designed primers in droplet digital PCR, benchmarked against 16S rRNA and shotgun sequencing. Our data shows that PUPpy-designed microbe-specific primers can be used to quantify substrain-level absolute counts, providing more resolved and accurate quantification in defined communities than short-read 16S rRNA and shotgun sequencing. IMPORTANCE: Profiling microbial communities at high resolution and with absolute quantification is essential to uncover hidden ecological interactions within microbial ecosystems. Nevertheless, achieving resolved and quantitative investigations has been elusive due to methodological limitations in distinguishing and quantifying highly related microbes. Here, we describe Phylogenetically Unique Primers in python (PUPpy), an automated computational pipeline to design taxon-specific primers within defined microbial communities. Taxon-specific primers can be used to selectively detect and quantify individual microbes and larger taxa within a microbial community. PUPpy achieves substrain-level specificity without the need for computationally intensive databases and prioritizes user-friendliness by enabling both terminal and graphical user interface applications. Altogether, PUPpy enables fast, inexpensive, and highly accurate perspectives into microbial ecosystems, supporting the characterization of bacterial communities in both in vitro and complex microbiota settings.

15.
J Arthroplasty ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972434

RESUMO

INTRODUCTION: In orthopaedic surgery, particularly total knee arthroplasty (TKA), the management of surgical wounds is critical for optimal wound healing and successful patient outcomes. Despite advances in surgical techniques, challenges persist in effectively managing surgical wounds to prevent complications and infections. This study aimed to identify and address the critical evidence gaps in wound management in TKA, including preoperative optimization, intraoperative options, and for the avoidance of postoperative complications. These are important issues surrounding wound management, which is essential for improving patient recovery and the overall success of the surgery. METHODS: Utilizing the Delphi method, this study brought together 20 experienced orthopaedic surgeons from Europe and North America. Conducted from April to September 2023, the process involved three stages: an initial electronic survey, a virtual meeting, and a concluding electronic survey. The panel reviewed and reached a consensus on 26 specific statements about wound management in TKA based on a comprehensive literature review. During these three stages and after further panel review, an alternative goal of the Delphi panel was to also identify critical evidence gaps in the current understanding of wound management practices for TKA. RESULTS: While the panel reached consensus on various wound management practices, they highlighted several major evidence gaps. Also, there was general consensus on issues such as wound closure methods including the use of mesh-adhesive dressings, skin glue, staples, sutures (including barbed sutures),and negative-pressure wound therapy (NPWT). However, it was deemed necessary that further evidence needs to be generated to address the cost-effectiveness of each and develop best practices for promoting patient outcomes. The identification of these gaps points to areas requiring more in-depth research and improvements to enhance wound care in TKA. DISCUSSION: The identification of these major evidence gaps underscores the need for targeted research in wound management surrounding TKA. Addressing these evidence gaps is crucial for the future development of more effective, efficient, and patient-friendly wound care strategies. Future research should prioritize these areas, focusing on comparative effectiveness studies and further developing clear guidelines for the use of emerging technologies. Bridging these gaps has the potential to improve patient outcomes, reduce complications, and elevate the overall success rate of TKA surgeries.

16.
J Manag Care Spec Pharm ; 30(7): 639-645, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38950159

RESUMO

Tralokinumab is the first selective interleukin 13 inhibitor approved for moderate to severe atopic dermatitis. This article reports the findings of a comprehensive literature review and extensive economic analysis to assess tralokinumab's safety, effectiveness, and cost. Evidence synthesis involved evaluating comparative effectiveness and conducting economic sensitivity analyses. This review was prepared by the University of Connecticut School of Pharmacy Academy of Managed Care Pharmacy (AMCP) Student Chapter. The student author group won the AMCP National Pharmacy and Therapeutics competition for their tralokinumab product review in March 2023.


Assuntos
Anticorpos Monoclonais , Análise Custo-Benefício , Dermatite Atópica , Humanos , Anticorpos Monoclonais/economia , Anticorpos Monoclonais/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/economia
17.
Artigo em Inglês | MEDLINE | ID: mdl-38991770

RESUMO

BACKGROUND AND PURPOSE: A single aspiration maneuver using a large volume syringe is a common and effective technique for aspiration thrombectomy. Multiple aspiration cycles using large aspiration syringes has been proposed as a means to improve efficacy over single aspiration. In this study, we sought to investigate the efficacy of a "triple aspiration technique" where a large volume syringe is cycled three times prior to catheter retraction during aspiration thrombectomy. MATERIALS AND METHODS: A 3D-printed adult vasculature was used as a benchtop thrombectomy platform. Fibrin-rich and red blood cell-rich clots were prepared in centrifuge tubes using human plasma, red blood cells, and calcium chloride. Next, clots were placed in the carotid terminus of the model, and the performances of three different aspiration techniques-triple syringe, single syringe, and continuous pump aspiration-were compared in a randomized manner (1:1:1). Outcomes of interest included first-pass efficacy (FPE), complete clot removal (final mTICI 2c/3), the number of thrombectomy attempts to achieve mTICI 2c/3, vacuum pressure, and distal embolization. The distal emboli were detected using a 70-micron cell strainer placed at the outflow of the model and quantified using an image processing algorithm. The vacuum pressures were measured using a pressure transducer (Honeywell, NC, USA). RESULTS: A total of 102 replicates were performed, 34 for each technique. The triple aspiration technique provided a significantly higher rate of FPE than the syringe and pump aspiration techniques (67.6% vs. 41.1%, p= 0.02). Additionally, the triple aspiration technique achieved complete clot removal with a significantly lower number of thrombectomy attempts compared to single syringe aspiration (1.2 ± 0.5 vs. 1.8 ± 0.8, p=0.005). The triple aspiration technique generated significantly higher vacuum pressure than both the single syringe and vacuum pump aspiration (28.3 ± 0.2 vs. 27.2 ± 0.3 (p= 0.002) and 26.2 ± 0.4 (p=0.001), respectively). The differences in complete clot removal and distal embolization parameters were not statistically significantly different across the groups. CONCLUSIONS: Our findings suggest that the triple aspiration technique can improve FPE rates and vacuum pressure in aspiration thrombectomy. Further studies are needed to examine the safety and efficacy of triple aspiration in the clinical setting. ABBREVIATIONS: AcommA = anterior communicating artery; FPE = first pass efficacy; ICA = internal carotid artery; MCA = middle cerebral artery; MT = mechanical thrombectomy; mTICI = modified thrombolysis in cerebral infarction scale; PcommA = posterior communicating artery.

18.
Respir Med ; 231: 107737, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38986792

RESUMO

BACKGROUND: Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi. METHODS: We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement. RESULTS: 78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal. CONCLUSIONS: Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients.

19.
J Am Chem Soc ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995837

RESUMO

We report on an electron donor-electron acceptor-stable radical (D-A-R•) molecule in which an electron spin state first prepared on R• is followed by photogeneration of an entangled singlet 1[D•+-A•-] spin pair to produce D•+-A•--R•. Since the A•- and R• spins within D•+-A•--R• are uncorrelated, spin teleportation from R• to D•+ occurs with a maximal 25% efficiency only for the singlet pair 1(A•--R•) by spin-allowed electron transfer from A•- to R•. However, since 1[D•+-A•-] is sufficiently long-lived, coherent spin mixing involving the unreactive 3(A•--R•) population affects entanglement and teleportation within D•+-A•--R•. Pulse electron paramagnetic resonance experiments show a direct correlation between electron spin flip-flops and entanglement loss, providing information for designing molecular materials to serve as nanoscale quantum device interconnects.

20.
Cureus ; 16(6): e62088, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38989349

RESUMO

Diazoxide is the only medication approved by the United States Food and Drug Administration for the treatment of hyperinsulinism-induced hypoglycemia. Overdose is infrequently reported. This case describes a preterm four-week-old male who was prescribed diazoxide and chlorothiazide for perinatal stress-induced hyperinsulinism. The patient presented to the emergency department with feeding intolerance and abdominal distension following an accidental 10-fold diazoxide overdose. On presentation, vital signs were remarkable for tachycardia and intermittent tachypnea. Physical exam revealed a grossly distended abdomen. Laboratory abnormalities included a glucose of 216 mg/dL, sodium of 132 mmol/L, and chloride of 98 mmol/L. Abdominal X-ray interpretation found moderate gaseous distension suggestive of generalized ileus. The patient was admitted to the neonatal intensive care unit (NICU), and a nasogastric tube was placed. He received intravenous dextrose fluids, and enteral feeds were resumed as serial X-rays showed interval improvement. The patient remained in the NICU for several days to monitor bowel movements and resolution of ileus and he was discharged after improvement. While diazoxide overdose is rarely reported, and ileus due to such is documented even less frequently, 10-fold medication dose errors are common among infants. The source of the 10-fold mistake is often decimal points, leading zeros, or trailing zeros. Utilizing the smallest possible syringe for the prescribed dose may reduce the incidence of medication errors.

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