Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 117
Filter
1.
Best Pract Res Clin Obstet Gynaecol ; : 102499, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38710608

ABSTRACT

Diaphragmatic endometriosis (DpE) is a rare disease localization which represents an important clinical challenge. The main criticisms toward the proper DpE management consist of poor consensus on both surgical indications and the choice between different surgical techniques available to treat the disease. Furthermore, only weak recommendations are provided by current guidelines and surgical management is mostly based on surgeon's experience. As consequence, the lack of standardization about the surgical treatment led to the risk of under- or over-treatments in patients suffering from this form of endometriosis. The latest evidence-based data suggest to adopt a lesion-oriented surgical approach serving as a guide in daily surgical activities, in order to ensure a tailored radicality and reduce the rate of surgery-related complications. Diaphragmatic endometriosis surgery should be performed only by expert surgeons with an extensive oncogynecologic expertise since it represents a technically demanding procedure. A multidisciplinary approach is also mandatory in order to adequately select and treat these patients by minimizing the risk of additional morbidity.

2.
Article in English | MEDLINE | ID: mdl-38698585

ABSTRACT

INTRODUCTION: While digital breast tomosynthesis (DBT) has proven to enhance cancer detection and reduce recall rates (RR), its integration into BreastScreen Australia for screening has been limited, in part due to perceived cost implications. This study aims to assess the cost effectiveness of digital mammography (DM) compared with synthesized mammography and DBT (SM + DBT) in a first round screening context for short-term outcomes. METHODS: Clients recalled for nonspecific density (NSD) as a single lesion by both readers at the Northern Sydney Central Coast BreastScreen service in 2019 were included. Prior images were excluded to simulate first-round screening. Eleven radiologists read DM and synthesized mammography with DBT (SM + DBT) images 4 weeks apart. Recall rates (RR), reading time, and diagnostic parameters were measured, and costs for screen reading and assessment were calculated. RESULT: Among 65 clients studied, 13 were diagnosed with cancer, with concordant cancer recalls. SM + DBT reduced recall rates (RR), increased reading time, maintained cancer detection sensitivity, and significantly improved other diagnostic parameters, particularly false positive rates. Benign biopsy recalls remained equivalent. While SM + DBT screen reading cost was significantly higher than DM (DM AU$890 ± 186 vs SM + DBT AU$1279 ± 265; P < 0.001), the assessment cost (DM AU$29,504 ± 9427 vs SM + DBT AU$18,021 ± 5606; P < 0.001), and combined screen reading and assessment costs were significantly lower (DM AU$30,394 ± 9508 vs SM + DBT AU$19,300 ± 5721; P = 0.001). SM + DBT screen reading and assessment of 65 patients resulted in noteworthy cost savings (AU$11,094), equivalent to assessing 12 additional clients. CONCLUSION: In first round screening, DBT yields significant cost savings by effectively reducing unnecessary recalls to assessment while maintaining diagnostic efficacy.

3.
Aust N Z J Obstet Gynaecol ; 64(2): 147-153, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37905841

ABSTRACT

BACKGROUND: Laparoscopic reverse submucosal dissection (LRSD) is a standardised surgical technique for removal of rectosigmoid endometriosis which optimises the anatomical dissection plane for excision of endometriotic nodules. AIM: This cohort study assesses the outcomes of the first cohort of women treated by LRSD, for deeply infiltrating rectosigmoid endometriosis. MATERIALS AND METHODS: Primary outcomes assessed were complication rate as defined by the Clavien-Dindo system, and completion of the planned LRSD. Secondary outcomes include mucosal breach, specimen margin involvement, length of hospital admission, and a comparison of pre-operative and post-operative pain, bowel function and quality of life surveys. These included the Endometriosis Health Profile Questionnaire (EHP-30), the Knowles-Eccersley-Scott Symptom Questionnaire (KESS) and the Wexner scale. RESULTS: Of 19 patients treated, one required a segmental resection. The median length of hospital admission was two days (range 1-5) and no post-operative complications occurred. Median pain visual analogue scales (scale 0-10) were higher prior to surgery (dysmenorrhoea 9.0, dyspareunia 7.5, dyschezia 9.0, pelvic pain 6.0) compared to post-surgical median scores (dysmenorrhoea 5.0, dyspareunia 4.0, dyschezia 2.0, pelvic pain 4.0) at a median of six months (range 4-32). Quality of life studies suggested improvement following surgery with pre-operative median EHP-30 and KESS scores (EHP-30: 85 (5-106), KESS score 9 (0-20)) higher than post-operative scores (EHP-30: 48.5 (0-80), KESS score: 3 (0-19)). CONCLUSION: This series highlights the feasibility of LRSD with low associated morbidity as a progression of partial thickness discoid excision (rectal shaving) for the treatment of rectosigmoid deep infiltrating endometriosis.


Subject(s)
Dyspareunia , Endometriosis , Laparoscopy , Rectal Diseases , Humans , Female , Endometriosis/surgery , Endometriosis/complications , Cohort Studies , Rectal Diseases/surgery , Dysmenorrhea/etiology , Quality of Life , Dyspareunia/etiology , Treatment Outcome , Laparoscopy/adverse effects , Laparoscopy/methods , Constipation/complications , Constipation/surgery , Postoperative Complications , Pelvic Pain/surgery , Pelvic Pain/complications
4.
J Antibiot (Tokyo) ; 77(3): 135-146, 2024 03.
Article in English | MEDLINE | ID: mdl-38114565

ABSTRACT

Cephalosporins comprise a ß-lactam antibiotic class whose first members were discovered in 1945 from the fungus Cephalosporium acremonium. Their clinical use for Gram-negative bacterial infections is widespread due to their ability to traverse outer membranes through porins to gain access to the periplasm and disrupt peptidoglycan synthesis. More recent members of the cephalosporin class are administered as last resort treatments for complicated urinary tract infections, MRSA, and other multi-drug resistant pathogens, such as Neisseria gonorrhoeae. Unfortunately, there has been a global increase in cephalosporin-resistant strains, heteroresistance to this drug class has been a topic of increasing concern, and tolerance and persistence are recognized as potential causes of cephalosporin treatment failure. In this review, we summarize the cephalosporin antibiotic class from discovery to their mechanisms of action, and discuss the causes of cephalosporin treatment failure, which include resistance, tolerance, and phenomena when those qualities are exhibited by only small subpopulations of bacterial cultures (heteroresistance and persistence). Further, we discuss how recent efforts with cephalosporin conjugates and combination treatments aim to reinvigorate this antibiotic class.


Subject(s)
Cephalosporin Resistance , Gram-Negative Bacterial Infections , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cephalosporins/pharmacology , Cephalosporins/therapeutic use , Gram-Negative Bacterial Infections/drug therapy , Neisseria gonorrhoeae , Monobactams/therapeutic use
5.
Philos Trans R Soc Lond B Biol Sci ; 379(1893): 20220263, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37952613

ABSTRACT

Global consciousness (GC), encompassing cosmopolitan orientation, global orientations (i.e. openness to multicultural experiences) and identification with all humanity, is a relatively stable individual difference that is strongly associated with pro-environmental attitudes and behaviours, less ingroup favouritism and prejudice, and greater pandemic prevention safety behaviours. Little is known about how it is socialized in everyday life. Using stratified samples from six societies, socializing institution factors correlating positively with GC were education, white collar work (and its higher income) and religiosity. However, GC also decreased with increasing age, contradicting a 'wisdom of elders' transmission of social learning, and not replicating typical findings that general prosociality increases with age. Longitudinal findings were that empathy-building, network-enhancing elements like getting married or welcoming a new infant, increased GC the most across a three-month interval. Instrumental gains like receiving a promotion (or getting a better job) also showed positive effects. Less intuitively, death of a close-other enhanced rather than reduced GC. Perhaps this was achieved through the ritualized management of meaning where a sense of the smallness of self is associated with growth of empathy for the human condition, as a more discontinuous or opportunistic form of culture-based learning. This article is part of the theme issue 'Evolution and sustainability: gathering the strands for an Anthropocene synthesis'.


Subject(s)
Cultural Evolution , Humans , Aged , Consciousness , Social Behavior , Prejudice , Cultural Diversity
6.
Sci Rep ; 13(1): 21413, 2023 12 04.
Article in English | MEDLINE | ID: mdl-38049436

ABSTRACT

While national parochialism is commonplace, individual differences explain more variance in it than cross-national differences. Global consciousness (GC), a multi-dimensional concept that includes identification with all humanity, cosmopolitan orientation, and global orientation, transcends national parochialism. Across six societies (N = 11,163), most notably the USA and China, individuals high in GC were more generous allocating funds to the other in a dictator game, cooperated more in a one-shot prisoner's dilemma, and differentiated less between the ingroup and outgroup on these actions. They gave more to the world and kept less for the self in a multi-level public goods dilemma. GC profiles showed 80% test-retest stability over 8 months. Implications of GC for cultural evolution in the face of trans-border problems are discussed.


Subject(s)
Consciousness , Cultural Evolution , Humans , Game Theory , Prisoner Dilemma , China , Cooperative Behavior
7.
Front Genet ; 14: 1308738, 2023.
Article in English | MEDLINE | ID: mdl-38090148

ABSTRACT

Genomic and personalized medicine implementation efforts have largely centered on specialty care in tertiary health systems. There are few examples of fully integrated care systems that span the healthcare continuum. In 2014, NorthShore University HealthSystem launched the Center for Personalized Medicine to catalyze the delivery of personalized medicine. Successful implementation required the development of a scalable family history collection tool, the Genetic and Wellness Assessment (GWA) and Breast Health Assessment (BHA) tools; integrated pharmacogenomics programming; educational programming; electronic medical record integration; and robust clinical decision support tools. To date, more than 225,000 patients have been screened for increased hereditary conditions, such as cancer risk, through these tools in primary care. More than 35,000 patients completed clinical genetic testing following GWA or BHA completion. An innovative program trained more than 100 primary care providers in genomic medicine, activated with clinical decision support and access to patient genetic counseling services and digital healthcare tools. The development of a novel bioinformatics platform (FLYPE) enabled the incorporation of genomics data into electronic medical records. To date, over 4,000 patients have been identified to have a pathogenic or likely pathogenic variant in a gene with medical management implications. Over 33,000 patients have clinical pharmacogenomics data incorporated into the electronic health record supported by clinical decision support tools. This manuscript describes the evolution, strategy, and successful multispecialty partnerships aligned with health system leadership that enabled the implementation of a comprehensive personalized medicine program with measurable patient outcomes through a genomics-enabled learning health system model that utilizes implementation science frameworks.

8.
Biochem Biophys Res Commun ; 679: 6-14, 2023 Oct 30.
Article in English | MEDLINE | ID: mdl-37651872

ABSTRACT

Aromatic amino acid decarboxylase is a pyridoxal 5'-phosphate-dependent enzyme responsible for the synthesis of the neurotransmitters, dopamine and serotonin. Here, by a combination of bioinformatic predictions and analyses, phosphorylation assays, spectroscopic investigations and activity measurements, we determined that Ser-193, a conserved residue located at the active site, can be phosphorylated, increasing catalytic efficiency. In order to determine the molecular basis for this functional improvement, we determined the structural and kinetic properties of the site-directed variants S193A, S193D and S193E. While S193A retains 27% of the catalytic efficiency of wild-type, the two acidic side chain variants are impaired in catalysis with efficiencies of about 0.15% with respect to the wild-type. Thus, even if located at the active site, Ser-193 is not essential for enzyme activity. We advance the idea that this residue is fundamental for the correct architecture of the active site in terms of network of interactions triggering catalysis. This role has been compared with the properties of the Ser-194 of the highly homologous enzyme histidine decarboxylase whose catalytic loop is visible in the spatial structure, allowing us to propose the validation for the effect of the phosphorylation. The effect could be interesting for AADC deficiency, a rare monogenic disease, whose broad clinical phenotype could be also related to post translational AADC modifications.

9.
Sci Rep ; 13(1): 9636, 2023 06 14.
Article in English | MEDLINE | ID: mdl-37316507

ABSTRACT

Type 2 diabetes mellitus (T2DM) patients show brain tissue changes in mood and cognitive regulatory sites, but the nature and extent of tissue injury and their associations with symptoms are unclear. Our aim was to examine brain tissue damage in T2DM over controls using mean diffusivity (MD) computed from diffusion tensor imaging (DTI), and assess correlations with mood and cognitive symptoms in T2DM. We collected DTI series (MRI), mood, and cognitive data, from 169 subjects (68 T2DM and 101 controls). Whole-brain MD-maps were calculated, normalized, smoothed, and compared between groups, as well as correlated with mood and cognition scores in T2DM subjects. Type 2 diabetes patients showed altered cognitive and mood functions over control subjects. Multiple brain sites in T2DM patients showed elevated MD values, indicating chronic tissue changes, including the cerebellum, insula, and frontal and prefrontal cortices, cingulate, and lingual gyrus. Associations between MD values and mood and cognition scores appeared in brain sites mediating these functions. Type 2 diabetes patients show predominantly chronic brain tissue changes in areas mediating mood and cognition functions, and tissue changes from those regions correlate with mood and cognitive symptoms suggesting that the microstructural brain changes may account for the observed functional deficits.


Subject(s)
Brain Injuries , Diabetes Mellitus, Type 2 , Humans , Adult , Diabetes Mellitus, Type 2/complications , Diffusion Tensor Imaging , Brain/diagnostic imaging , Cognition
10.
Fam Cancer ; 22(4): 499-511, 2023 10.
Article in English | MEDLINE | ID: mdl-37335380

ABSTRACT

Young women with Neurofibromatosis type 1 (NF1) have a high risk of developing breast cancer and poorer survival following breast cancer diagnosis. International guidelines recommend commencing breast screening between 30 and 35 years; however, the optimal screening modality is unestablished, and previous reports suggest that breast imaging may be complicated by the presence of intramammary and cutaneous neurofibromas (cNFs). The aim of this study was to explore potential barriers to implementation of breast screening for young women with NF1.Twenty-seven women (30-47 years) with NF1 completed breast screening with breast MRI, mammogram and breast ultrasound. Nineteen probably benign/suspicious lesions were detected across 14 women. Despite the presence of breast cNFs, initial biopsy rate for participants with NF1 (37%), were comparable to a BRCA pathogenic variant (PV) cohort (25%) (P = 0.311). No cancers or intramammary neurofibromas were identified. Most participants (89%) returned for second round screening.The presence of cNF did not affect clinician confidence in 3D mammogram interpretation, although increasing breast density, frequently seen in young women, impeded confidence for 2D and 3D mammogram. Moderate or marked background parenchymal enhancement on MRI was higher in the NF1 cohort (70.4%) than BRCA PV carriers (47.3%), which is an independent risk factor for breast cancer.Breast MRI was the preferred mode of screening over mammogram, as the majority (85%) with NF1 demonstrated breast density (BI-RADS 3C/4D), which hinders mammogram interpretation. For those with high breast density and high cNF breast coverage, 3D rather than 2D mammogram is preferred, if MRI is unavailable.


Subject(s)
Breast Neoplasms , Neurofibromatosis 1 , Female , Humans , Neurofibromatosis 1/diagnostic imaging , Retrospective Studies , Breast/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Mammography/methods , Magnetic Resonance Imaging/methods
11.
Nurs Res ; 72(6): 495-501, 2023.
Article in English | MEDLINE | ID: mdl-37199499

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent in patients with Type 2 diabetes, more so in veterans compared with nonveterans. Positive airway pressure is the recommended first-line treatment for OSA. However, adherence to both positive airway pressure and diabetes management regimens can be challenging for older adults. Support from family or friends may improve glucose control or sleep-apnea-related symptoms, yet the evidence is limited when both conditions coexist. OBJECTIVES: This study aimed to describe veterans' experiences of support from family and friends with managing comorbid sleep apnea and Type 2 diabetes. METHODS: We conducted a postal survey of older veterans with OSA and Type 2 diabetes from one healthcare system. Questions include demographic and health-related information, information about sleep apnea and diabetes treatment and education received, related support from family or a friend, perceived benefits of regular positive airway pressure device use on improving sleep health, and perceived benefits of education for family or a friend on sleep apnea and diabetes. Descriptive and bivariate analyses were performed. RESULTS: Of 145 respondents (mean age = 72 years), 43% reported receiving help for Type 2 diabetes from family or a friend. Almost two thirds of the respondents were currently using a positive airway pressure device, of whom 27% received support with device use from family or friends. About one third of veterans perceived family and friends receiving education on treating sleep apnea and diabetes to be very or extremely helpful. Such perceived benefit was higher among those who were married or identified as non-White. Veterans using a positive airway pressure device had lower hemoglobin A1c levels than nonusers. DISCUSSION: Veterans perceived that additional education for the individuals providing support would be beneficial. Future studies could address interventions to increase sleep apnea and Type 2 diabetes knowledge among families and friends of veterans with these comorbid conditions. In addition, patients' adherence to positive airway pressure may be enhanced by support from family and friends.


Subject(s)
Diabetes Mellitus, Type 2 , Sleep Apnea, Obstructive , Veterans , Humans , Aged , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Continuous Positive Airway Pressure , Sleep Apnea, Obstructive/therapy , Sleep
12.
West J Nurs Res ; 45(8): 745-753, 2023 08.
Article in English | MEDLINE | ID: mdl-37151052

ABSTRACT

Chronic illnesses among Korean immigrants (KIs) in the United States have been rapidly increasing, yet the concept of chronic disease self-care in this group has not been delineated. The aim of this study was to review previous research on self-care among KIs with chronic diseases and describe the concept in cultural context. Using Rodgers' Evolutionary Method, a total of 24 articles were analyzed. The definition and conceptual model of self-care in KIs with chronic diseases were proposed. The antecedents included knowledge and health literacy; social and family support; resources; patient-health care provider partnership; and elimination of cultural misbeliefs and disclosure of the disease. The attributes of the concept were aging well with diseases; treatment adherence; control and restriction; the acculturation process; care built on traditional Korean gender roles; and maintenance of mental health. The consequences involved positive physiological outcomes; self-efficacy; quality of life; and reducing worry about becoming a burden to the family. While the studied concept encompassed universal characteristics of chronic disease self-care, distinctive cultural features emerged. The findings contribute to a better understanding of chronic illness self-care in this population and the development of culturally sensitive and practical self-care interventions for KIs with chronic diseases.


Subject(s)
Emigrants and Immigrants , Quality of Life , Humans , United States , Self Care , Chronic Disease , Republic of Korea
13.
Curr Opin Endocrinol Diabetes Obes ; 30(1): 7-13, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36385094

ABSTRACT

PURPOSE OF REVIEW: To review the connection between type 2 diabetes and cognitive dysfunction, including its epidemiology, potential mechanisms of pathophysiology, risk factors, possible prevention, and treatment considerations. RECENT FINDINGS: Diabetes is a risk factor for mild cognitive decline, in addition to Alzheimer's disease and vascular dementia. Duration of diabetes, concomitant vascular or associated co-morbidities, hyper- and hypoglycemia may lead to worsening cognitive dysfunction. Unfortunately, there is a lack of evidence-based guidance on the prevention of cognitive dysfunction in the diabetes population. Studies of diabetes medications, including metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 inhibitors (SGLT2) have shown some benefit with cardiovascular morbidity and may affect cognition. In the absence of clearly defined preventive tools, diabetes practice guidelines recommend annual cognitive screening as standard of care in adults with diabetes aged 65 years or older. SUMMARY: People living with diabetes are at risk for significant decline in cognitive function. Epidemiology and risk factors are well defined. Prevention and treatment strategies are limited and require further study.


Subject(s)
Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Adult , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Hypoglycemic Agents/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Risk Factors , Cognition , Glucagon-Like Peptide-1 Receptor/agonists
14.
Am J Perinatol ; 2022 Dec 05.
Article in English | MEDLINE | ID: mdl-36241211

ABSTRACT

OBJECTIVE: The aim of Placental Assessment in Response to Environmental Pollution Study (PARENTs) was to determine whether imaging of the placenta by novel multiparametric magnetic resonance imaging (MRI) techniques in early pregnancy could help predict adverse pregnancy outcomes (APOs) due to ischemic placental disease (IPD). Additionally, we sought to determine maternal characteristics and environmental risk factors that contribute to IPD and secondary APOs. STUDY DESIGN: Potential patients in their first trimester of pregnancy, who agreed to MRI of the placenta and measures of assessment of environmental pollution, were recruited into PARENTs, a prospective population-based cohort study. Participants were seen at three study visits during pregnancy and again at their delivery from 2015 to 2019. We collected data from interviews, chart abstractions, and imaging. Maternal biospecimens (serum, plasma, and urine) at antepartum study visits and delivery specimens (placenta, cord, and maternal blood) were collected, processed, and stored. The primary outcome was a composite of IPD, which included any of the following: placental abruption, hypertensive disease of pregnancy, fetal growth restriction, or a newborn of small for gestational age. RESULTS: In this pilot cohort, of the 190 patients who completed pregnancy to viable delivery, 50 (26%) developed IPD. Among demographic characteristics, having a history of prior IPD in multiparous women was associated with the development of IPD. In the multiple novel perfusion measurements taken of the in vivo placenta using MRI, decreased high placental blood flow (mL/100 g/min) in early pregnancy (between 14 and 16 weeks) was found to be significantly associated with the later development of IPD. CONCLUSION: Successful recruitment of the PARENTs prospective cohort demonstrated the feasibility and acceptability of the use of MRI in human pregnancy to study the placenta in vivo and at the same time collect environmental exposure data. Analysis is ongoing and we hope these methods will assist researchers in the design of prospective imaging studies of pregnancy. KEY POINTS: · MRI was acceptable and feasible for the study of the human placenta in vivo.. · Functional imaging of the placenta by MRI showed a significant decrease in high placental blood flow.. · Measures of environmental exposures are further being analyzed to predict IPD..

15.
J Orthop Case Rep ; 12(3): 56-60, 2022 Mar.
Article in English | MEDLINE | ID: mdl-36199922

ABSTRACT

Introduction: Deep vein thrombosis (DVTs) in children is rare, normally linked to pathologies such as major traumatic injury, thrombophilia, and malignancy. Osteonecrosis is still poorly understood. There is growing support to include hypercoagulable states as a predisposing factor, however, no definitive correlation has been found. At present, there are no conclusive literature on the links between osteonecrosis and DVT. Case Presentation: This report describes an unusual and rare case of osteonecrosis and idiopathic DVT in an 11-year-old girl who initially presented with a sprained left ankle. On follow-up, pain was persistent and subsequent radiological investigations revealed extensive DVT, and magnetic resonance imaging scan revealed osteonecrosis of the distal left tibia. Initial blood tests were normal, however with follow-up with hematology, a diagnosis of antithrombin deficiency was made, with the treatment of lifelong anticoagulation. Our patient had continued orthopedic input for clinical and radiographic surveillance to monitor leg length discrepancy. Conclusion: This case highlights the need to engage in close follow-up and the cautionary care required when young children present with non-resolving severe pain, to consider osteonecrosis and DVT. Our case also highlights the need for further research into the relationship between minor injuries and DVTs and osteonecrosis in children, and the potential synergistic relationship between DVTs and osteonecrosis.

16.
Cancer Immunol Res ; 10(12): 1441-1461, 2022 12 02.
Article in English | MEDLINE | ID: mdl-36129967

ABSTRACT

Immune-stimulator antibody conjugates (ISAC) combining tumor-targeting monoclonal antibodies with immunostimulatory agents allow targeted delivery of immune activators into tumors. NJH395 is a novel, first-in-class ISAC comprising a Toll-like receptor 7 (TLR7) agonist conjugated to an anti-HER2 antibody via a noncleavable linker payload. Preclinical characterization showed ISAC-mediated activation of myeloid cells in the presence of antigen-expressing cancer cells, with antigen targeting and TLR7 agonism contributing to antitumor activity. Safety, efficacy, immunogenicity, pharmacokinetics, and pharmacodynamics were investigated in a phase I, multicenter, open-label study in patients with HER2+ non-breast advanced malignancies (NCT03696771). Data from 18 patients enrolled in single ascending dose escalation demonstrated delivery of the TLR7-agonist payload in HER2+ tumor cells and induction of type I IFN responses, which correlated with immune modulation in the tumor microenvironment. Cytokine release syndrome was a common, but manageable, drug-related adverse event. Antidrug antibodies and neuroinflammation at high doses represented significant clinical challenges. Data provide proof-of-mechanism and critical insights for novel immunotherapies.


Subject(s)
Antineoplastic Agents, Immunological , Antineoplastic Agents , Immunoconjugates , Neoplasms , Humans , Toll-Like Receptor 7/agonists , Immunoconjugates/adverse effects , Neoplasms/drug therapy , Antineoplastic Agents, Immunological/therapeutic use , Receptor, ErbB-2 , Tumor Microenvironment
17.
HGG Adv ; 3(4): 100134, 2022 Oct 13.
Article in English | MEDLINE | ID: mdl-36039118

ABSTRACT

Achieving health equity in precision medicine remains a critical challenge because of the continued underrepresentation of non-white populations in research and barriers to genetic services. The goal of this study was to explore Vietnamese American (VA) participant views toward incorporating genetics in routine healthcare to better serve the local VA community within an integrated health system offering primary care-based population genetic testing to adults for conditions that could be prevented or mitigated when detected early. We conducted semi-structured interviews from August-September 2021, with 22 individuals receiving primary care who self-identified as Vietnamese or VA, and employed rapid qualitative analysis (RQA) to identify key concepts. Community research team members participated in study design, data collection, RQA, and reporting. Findings from the interviews revealed that several participant perceived challenges to genetic testing, which included lack of information, fear of results impact, cost, and privacy concerns. Participants suggested various ways to overcome some of these barriers, such as decreasing the cost of testing, receiving information from a trusted physician, using preferred education strategies in the community, and having convenient access to testing. Study participants also shared a variety of trusted sources they would seek out for advice on genetic testing. This study with VAs identified barriers, facilitators, and messengers to offering genetic testing in a local healthcare context and demonstrated how community-engaged research coupled with RQA is a promising approach for healthcare institutions as they identify needs and tailor strategies for implementing population genetic screening programs in local ethnic communities.

18.
ACS Appl Mater Interfaces ; 14(32): 36557-36569, 2022 Aug 17.
Article in English | MEDLINE | ID: mdl-35917313

ABSTRACT

Enhancement of redox-reversibility in electroactive species has been studied because of fundamental interest and their importance for energy storage systems. Various electroactive molecules suffer from redox-irreversible behavior, and this is a critical reason for their exclusion as redox electrolytes in energy storage systems. In this article, we fully demonstrated that ascorbic acid (ASC), which is an abundant but redox-irreversible molecule, can become redox-reversible when it is confined in microporous carbon regimes. From a theoretical perspective, redox-reversibility in an electrochemical reaction coupled with an irreversible chemical process can be greatly enhanced due to kinetic acceleration toward the inverse direction of the chemical reaction by accumulation of products in the nanoconfined regime. However, the kinetic acceleration in a nanoconfined domain shows limitations for enhancing the redox-reversibility, which indicates that stabilization of the species undergoing an irreversible chemical process is another important factor for redox-reversibility enhancement. The origin of nanoporous confinement of ASC and its enhanced redox-reversibility was rationalized by molecular dynamics simulations. We found that ASC-clusters of a fully protonated ASC and its conjugated base formed inside carbon pores, which would be a main driving force for its confinement in microporous carbon networks. Lastly, we demonstrated a prototype energy storage device using redox-reversible ASC in microporous carbon as the half electrode, which shows the feasibility of ASC as a possible redox electrolyte in an aqueous energy storage system.

19.
Res Gerontol Nurs ; 15(4): 193-202, 2022.
Article in English | MEDLINE | ID: mdl-35609258

ABSTRACT

Despite poor sleep among older adults, little is known about the sleep habits of older immigrants living in the United States. The current pragmatic qualitative descriptive study explored sleep among older Korean immigrants, using a focus group with six participants and individual phone interviews with 22 Korean immigrants aged ≥60 years. Transcripts were coded to identify underlying themes. Several thematic categories were identified under six domains: daytime function, getting ready for bed, falling asleep, awakenings during sleep, going back to sleep, and seeking advice from peers. Unhealthy sleep behaviors were found during daytime and bedtime, particularly among those who were retired/unemployed or living alone. Seeking advice from peers was common but none of the advice helped participants sleep. Sleep education programs in Korean-speaking communities can be used to target those who are socially isolated and may benefit older Korean immigrants with sleep difficulties. [Research in Gerontological Nursing, 15(4), 193-202.].


Subject(s)
Emigrants and Immigrants , Sleep Wake Disorders , Aged , Focus Groups , Humans , Qualitative Research , Republic of Korea , United States
20.
WMJ ; 121(1): 41-47, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35442578

ABSTRACT

BACKGROUND: Due to the COVID-19 pandemic, many genetics clinics across the country were prompted to integrate telephone visits and videoconferencing into their practice to promote the safety of patients and clinic staff members. Our study examined providers' perspectives on the utility and effectiveness of these telehealth-based clinic visits in response to the COVID-19 pandemic in Wisconsin. METHODS: An anonymous Qualtrics survey was distributed via email in October 2020 to all members of the Wisconsin Genetic Systems Integration Hub and the Wisconsin Genetic Counselor Association. Current clinical genetic providers were eligible to participate in the survey. The survey assessed providers' experiences and perceptions toward utilizing telehealth in delivering clinical genetic services to their patients during the pandemic. RESULTS: Forty-seven currently practicing clinical genetic counselors in Wisconsin either partially or fully completed the survey. Nearly all respondents somewhat (23%) or strongly (75%) wanted to incorporate telehealth in the future, primarily because of perceived improvements in clinic functioning. Patients with suboptimal telecommunications capacities were considered the most challenging aspect of telehealth, and better technology support was the most frequently cited strategy for addressing current telehealth limitations. CONCLUSION: Clinical genetic counselors in Wisconsin generally reported positive experiences integrating telehealth into their patient care during the COVID-19 pandemic. Many counselors see telehealth as a way to increase access to genetic services and, with better technology support from their intuitions, would support utilizing telehealth in their clinical practice.


Subject(s)
COVID-19 , Counselors , Telemedicine , COVID-19/epidemiology , Humans , Pandemics , Wisconsin/epidemiology
SELECTION OF CITATIONS
SEARCH DETAIL
...