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1.
J Med Internet Res ; 26: e64092, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39357049

RESUMO

BACKGROUND: Digital interventions to improve retention in HIV care are critical to ensure viral suppression and prevent further transmission. AIDS Healthcare Foundation Healthcare Centers are centers across the United States that provide primary HIV care. Traditionally, the Healthcare Centers conduct phone calls with patients to schedule and confirm appointments, as well as share laboratory results. In 2017, Healthvana piloted a digital platform at AIDS Healthcare Foundation Healthcare Centers to send patients SMS text message appointment reminders and allow patients to review their upcoming appointment and view their laboratory results in the web-based patient portal. OBJECTIVE: A national implementation in 15 US states and Washington, DC, of this digital intervention pilot by Healthvana aims to determine whether SMS appointment reminders and web-based patient portal logins improved retention in care compared to traditional methods. METHODS: A retrospective analysis of 40,028 patients living with HIV was conducted at the 61 AIDS Healthcare Foundation Healthcare Centers between January 2, 2017, and May 22, 2018. Patients were invited to enroll in Healthvana's digital intervention pilot, allowing for a natural, organization-wide case-control study. Separate binary logistic regression models evaluated the relationship between receiving SMS appointment reminders and completing scheduled appointments, as well as the relationship between logging into the web-based patient portal and completing scheduled appointments. Four scheduled consecutive appointments for each patient were included in the analysis to account for 1 full year of data per patient. RESULTS: Patients who received the SMS appointment reminder were 1.7 times more likely to complete appointment 1 compared to patients who did not receive the SMS appointment reminder (P<.001). In addition, patients who received the SMS appointment reminder were 1.6 times more likely to complete appointment 2 (P<.001), 1.7 times more likely to complete appointment 3 (P<.001), and 1.8 times more likely to complete appointment 4 (P<.001) compared to patients who did not receive the SMS appointment reminder. Patients who logged in to the web-based patient portal prior to their scheduled appointment were 7.4 times more likely to complete appointment 1 compared to patients who did not log in (P<.001). In addition, patients who logged in to the web-based patient portal prior to their scheduled appointment were 3.6 times more likely to complete appointment 2 (P<.001), 3.2 times more likely to complete appointment 3 (P<.001), and 2.8 times more likely to complete appointment 4 (P<.001) compared to patients who did not log in. CONCLUSIONS: HIV primary care appointment completion was higher when patients engaged with Healthvana's digital platform. Digital technology interventions to ensure patients complete their scheduled HIV care appointments are imperative to curb the HIV epidemic.


Assuntos
Infecções por HIV , Internet , Atenção Primária à Saúde , Humanos , Infecções por HIV/terapia , Estudos de Casos e Controles , Atenção Primária à Saúde/estatística & dados numéricos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Sistemas de Alerta/estatística & dados numéricos , Participação do Paciente/estatística & dados numéricos , Participação do Paciente/métodos , Agendamento de Consultas , Estudos Retrospectivos , Envio de Mensagens de Texto/estatística & dados numéricos , Estados Unidos , Portais do Paciente/estatística & dados numéricos , Retenção nos Cuidados/estatística & dados numéricos
2.
PNAS Nexus ; 3(10): pgae446, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39430221

RESUMO

Uterine contraction patterns vary during the ovulatory cycle and throughout pregnancy, but prior measurements have produced limited and conflicting information on these patterns. We combined a virally delivered genetically encoded calcium reporter (GCaMP8m) and ultra-widefield imaging in live nonpregnant mice to characterize uterine calcium dynamics at organ scale throughout the estrous cycle. Prior to ovulation (proestrus and estrus), uterine excitations primarily initiated in a region near the oviduct, but after ovulation (metestrus and diestrus), excitations initiated at loci homogeneously distributed throughout the organ. The frequency of excitation events was lowest in proestrus and estrus, higher in metestrus, and highest in diestrus. These results establish a platform for mapping uterine activity and demonstrate that an anatomically localized trigger for uterine excitations depends on the estrous cycle phase.

4.
ACS Nano ; 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39463189

RESUMO

Biomarkers detection has become essential in medical diagnostics and early detection of life-threatening diseases. Modern-day medicine relies heavily on painful and invasive tests, with the extraction of large volumes of venous blood being the most common tool of biomarker detection. These tests are time-consuming, complex, expensive and require multiple sample manipulations and trained staff. The application of "intradermal" biosensors utilizing microneedles as minimally invasive sensing elements for capillary blood biomarkers detection has gained extensive interest in the past few years as a central point-of-care (POC) detection platform. Herein, we present a diagnosis paradigm based on vertically aligned nanopillar array-embedded microneedles sampling-and-detection elements for the direct optical detection and quantification of biomarkers in capillary blood. We present here a demonstration of the simple fabrication route for the creation of a multidetection-zone silicon nanopillar array, embedded in microneedle elements, followed by their area-selective chemical modification, toward the multiplex intradermal biomarkers detection. The utilization of the rapid and specific antibody-antigen binding, combined with the intrinsically large sensing area created by the nanopillar array, enables the simultaneous efficient ultrafast and highly sensitive intradermal capillary blood sampling and detection of protein biomarkers of clinical relevance, without requiring the extraction of blood samples for the ex vivo biomarkers analysis. Through preliminary in vitro and in vivo experiments, the direct intradermal in-skin blood extraction-free platform has demonstrated excellent sensitivity (low pM) and specificity for the accurate multiplex detection of protein biomarkers in capillary blood.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39465549

RESUMO

Materials possessing multiple properties and functionalities, that can be controlled or modulated by external stimuli, are a central focus of current research in materials sciences due to their potential to significantly enhance various future technological applications. Herein, we report a significant advancement in this field through the development of a smart, multifunctional organomagnetic composite material. By utilizing a thin layer of polydimethylsiloxane (PDMS) and polypyrrole (PPy) precursors, doped with nickel nanoparticles (NiNPs), we have created an innovative organomagnetic, PDMS/PPy/NiNPs (PPN), single-layer composite film that displays multistimuli responsivity. The study presents the first demonstration of a multifunctional flexible, three-component film structure integrating the structural and flexible PDMS component, together with a conductive polymer component and metal-based nanoparticles into a single-layer design, which displays enhanced and unprecedented responsivity properties against multiple different stimuli. Unlike typical stacked multilayered structures, that exhibit one or two functionalities at most, this novel configuration exhibits multiple functionalities, including magnetoresistance, mechanical stress response, piezoresistivity, and temperature change sensitivity. The as-prepared film demonstrates notable magnetoresistance responsivity, with a relative electrical resistance, ΔR/R0, changing under a weak magnetic field and under ambient conditions. The significance of our study lies in the film's versatility, stability, and sensitivity, especially within the physiological temperature range, making it highly relevant for future biomedical applications. Furthemore, the film's sensitivity to mechanical deformation reveals an impressive piezoresistance behavior. Unlike existing multilayer architectures of higher complexity, our single-layer thin film offers a simpler, more flexible, and reliable solution with a broad range of stimuli-sensing capabilities. The significance of this novel multiresponsive composite material is underscored by the growing demand for advanced materials in biomedical devices, magnetic switches, sensors, electronic skin, transistors, and organic spintronic devices. These promising organomagnetic self-standing layers provide a robust platform for future technological innovations.

6.
BMC Infect Dis ; 24(1): 1128, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39385077

RESUMO

BACKGROUND: Identifying risk factors for respiratory syncytial virus (RSV)-associated severe acute respiratory illness (SARI) will assist with targeting vaccine interventions. METHODS: Using surveillance data from South Africa (2012-2018), we compared the characteristics of individuals with RSV-associated influenza-like illness (ILI) (reference group) to those with RSV-associated SARI to describe factors associated with SARI using a multivariable analysis. RESULTS: RSV was detected in 6% (483/7792) of ILI cases and 15% (844/5672) of SARI cases. Factors associated with SARI in children included age < 2 months, compared to age 2-4 years (adjusted odds ratio (aOR) 54.4; 95% confidence interval (CI) 23.5-125.8), malnutrition (aOR 1.9; 95% CI 1.2-3.2), prematurity (aOR 2.4; 95% CI 1.3-4.6) and living with HIV (LWH) (aOR 22.5; 95% CI 2.9-174.3). In individuals ≥ 5 years, factors associated with SARI included age ≥ 65 years compared to age 5-24 years (aOR 10.7; 95% CI 1.1-107.5), symptom duration ≥ 5 days (aOR 2.7; 95% CI 1.1-6.3), underlying illness (aOR 2.7; 95% CI 1.5-26.1) and LWH (aOR 16.8, 95% CI: 4.8-58.2). CONCLUSION: Individuals at the extremes of age and those with identified risk factors might benefit most from RSV prevention interventions. CLINICAL TRIAL NUMBER: Not applicable, this is not a clinical trial.


Assuntos
Infecções por HIV , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Humanos , África do Sul/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Fatores de Risco , Feminino , Lactente , Pré-Escolar , Masculino , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Adulto , Criança , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Prevalência , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Recém-Nascido , Idoso
7.
J Pediatr Urol ; 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39482187

RESUMO

INTRODUCTION: While not entirely understood, nocturnal enuresis (NE) has been considered pathophysiologically distinct from other non-neurogenic voiding disorders. We believe that a significant component of the pathology is due to bladder overactivity. Intravesical Onabotulinumtoxin A (OBTA) injections are utilized in overactive bladder management. We hypothesized that OBTA injections would be efficacious for NE management in pediatric patients with symptoms refractory to conventional therapies. MATERIALS AND METHODS: A retrospective cohort analysis of patients <18-years-old with primary NE who underwent OBTA injections was performed. Injections were performed by a single surgeon at a single tertiary referral center per standardized protocol. Treatment response was defined as no improvement, greater than 50 % improvement in nightly accidents, or complete resolution of accidents. The primary outcome was treatment success, defined as greater than 50 % improvement in nightly accidents or complete resolution. Secondary outcomes included treatment response duration and complication data. Descriptive and bivariate statistics were performed as indicated. A Kaplan Meier analysis was performed to assess failure free survival following OBTA injection. RESULTS: Fifty patients met inclusion criteria for this analysis. All patients had trialed at least one lifestyle modification, a bowel regimen, and at least two medications with symptom persistence. The median post-procedure follow-up time was 9.5 months (range 2-82). Improvement in incontinence symptoms compared to pre-operative baseline was seen in 94.0 % of patients, with 58.0 % demonstrating complete resolution of incontinence through most recent follow up. There was no difference in improvement rates or resolution rates in male vs female gender. The median failure free survival identified on Kaplan Meier analysis was 12.5 months (Figure 1) Minor post-operative complications (4 urinary tract infections; 1 retentive episode necessitating catheterization) were identified in five patients. There were no major post-operative complications. DISCUSSION: Efficacy of OBTA injections was high, with treatment success demonstrated in 94 % of patients and failure free survival of 12.5 months. This procedure also demonstrated a favorable safety profile, with few minor post-operative complications identified. These results indicate that this procedure may be a beneficial therapeutic option for patients with NE refractory to multiple lines of conventional therapy. This study is limited by its retrospective design with short median follow up and potential for recall bias. It is strengthened by its large sample size and novelty. CONCLUSIONS: To our knowledge, this is the first analysis of the efficacy of OBTA injections for management of primary NE. A follow up clinical trial is essential to further understand this association.

8.
Artigo em Inglês | MEDLINE | ID: mdl-39478188

RESUMO

With a prolonging duration of survivorship, patients with multiple myeloma (MM) who receive high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) have an increased risk of secondary malignancy, most concerning acute leukemia. We retrospectively reviewed the records of all patients with MM who underwent auto-HCT between January 1, 2010, and January 1, 2023, who later developed therapy-related acute leukemia (t-AL). Of 1770 patients with MM who underwent auto-HCT, 18 (1.01%) developed t-AL at a mean interval of 60.0 ± 41.3 months after auto-HCT. The patients with t-AL consisted of 9 (50%) with B-cell acute lymphoblastic leukemia (B-ALL), 8 (44.4%) with acute myeloid leukemia (AML), and 1 (5.6%) with acute promyelocytic leukemia (APML). All patients had received an alkylating agent as part of induction, and the majority received lenalidomide as maintenance therapy. Genetic abnormalities of t-AL were consistent with prior reports. Median overall survival from diagnosis of t-AL was 19.5 months. In patients with t-AL who entered CR, long term survival was common. Further research on predisposing conditions to developing t-AL in patients with MM undergoing auto-HCT is warranted.

9.
BJUI Compass ; 5(10): 934-941, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39416760

RESUMO

Objectives: To analyse the presentation, management and long-term outcomes of renal transplant patients who formed kidney stones in their allograft. The secondary aim was to identify risk factors for stone formation in this cohort. Materials and Methods: Patient information from an institutional renal transplant database was used to identify individuals who both did and did not form kidney stones following renal transplantation. Computerized tomography (CT) imaging was used to make the diagnosis of kidney stones and measure stone size. Age- and gender-matched controls never forming a stone in their allograft were used for comparative analysis to identify risk factors for stone formation in transplant patients. Results: A total of 8835 transplant patients were included in the study, of which 128 (1.4%) formed a kidney stone in their allograft after surgery. The mean time to kidney stone identification was 6.2 years, and the mean number of stones formed was 1.7, with a mean maximum size dimension on a CT scan of 5.7 mm per stone. A total of 26 patients were subjected to stone-removing procedures, the most common being ureteroscopy (42.3%). The primary intervention failed in eight patients requiring a secondary intervention, and percutaneous nephrolithotomy (PCNL) had the lowest success rate (60%). A total of 164 controls were identified. In comparison to controls, stone formers had lower serum calcium (p = 0.008), lower estimated glomerular filtration rates (p = 0.019), higher lymphocyte counts (p = 0.021) and greater rate of urinary tract infection (p = 0.003). Graft failure rates were the same (p = 0.524), but time to graft failure was significantly longer in stone patients compared with controls (p = 0.008). Conclusions: The rate of stone formation is low in transplant patients. Success rates for stone treatment vary based on the surgery selected, with PCNL being the worst. Graft survival rates were equivocal, but survival time was better in stone patients. Our analysis calls for further investigation of this important topic.

10.
MMWR Morb Mortal Wkly Rep ; 73(42): 950-954, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39446669

RESUMO

Legionnaires disease is a serious pneumonia caused by Legionella bacteria. During November 2022-June 2024, CDC was notified of 12 cases of Legionnaires disease among travelers on two cruise ships; eight on cruise ship A and four on cruise ship B. CDC, in collaboration with the cruise lines, initiated investigations to ascertain the potential sources of on-board exposure after notification of the second potentially associated case for each ship. Epidemiologic data collected from patient interviews and environmental assessment and sampling results identified private hot tubs on selected cabin balconies as the most likely exposure source. To minimize Legionella growth, both cruise lines modified the operation and maintenance of these devices by removing the heating elements, draining water between uses, and increasing the frequency of hyperchlorination and cleaning. Hot tubs offer favorable conditions for Legionella growth and transmission when maintained and operated inadequately, regardless of location. Private hot tubs on cruise ships are not subject to the same maintenance requirements as are public hot tubs in common areas. Given the range of hot tub-type devices offered as amenities across the cruise industry, to reduce risk for Legionella growth and transmission, it is important for cruise ship water management program staff members to inventory and assess private balcony hot tubs and adapt public hot tub maintenance and operations protocols for use on private outdoor hot tubs.


Assuntos
Surtos de Doenças , Doença dos Legionários , Navios , Humanos , Doença dos Legionários/epidemiologia , Pessoa de Meia-Idade , Masculino , Adulto , Feminino , Microbiologia da Água , Idoso , Adulto Jovem
11.
Blood ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39321344

RESUMO

Adoptive T cell therapy is a promising therapy for multiple myeloma (MM), but its efficacy hinges on understanding relevant biological and predictive markers of response. B cell maturation antigen (BCMA) is a key target antigen in MM, with active development of multiple anti-BCMA T cell engagers (TCE) and chimeric antigen receptor T cell (CAR T) therapies. The regulation of surface BCMA expression by MM cells, resulting in the shedding of soluble BCMA (sBCMA), has triggered debate surrounding the significance of sBCMA as a predictive marker and its potential impact on treatment outcomes. In order to address this, we leveraged whole genome sequencing and in vitro assays to demonstrate that sBCMA may independently predict primary refractoriness to anti-BCMA therapies. In addition to sBCMA, tumor burden and surface BCMA antigen density collectively influence anti-BCMA TCE cytotoxic efficacy. Correlative analyses of 163 patients treated with anti-BCMA TCE teclistamab validated and further underscored the association between elevated baseline sBCMA (>400 ng/mL) and refractoriness. Importantly, increasing TCE dose, the use of TCE against alternative targets (e.g.,GPRC5D), or gamma secretase inhibitors were able to overcome high sBCMA. These findings highlight the importance of accounting for baseline sBCMA levels, disease burden, and TCE dose intensity when administering anti-BCMA TCEs, offering critical insights for optimizing therapeutic strategies to overcome specific high-risk features and primary anti-BCMA TCE refractoriness.

12.
MMWR Morb Mortal Wkly Rep ; 73(36): 793-798, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264843

RESUMO

On June 17, 2024, the Food and Drug Administration approved 21-valent pneumococcal conjugate vaccine (PCV) (PCV21; CAPVAXIVE; Merck Sharp & Dohme, LLC) for adults aged ≥18 years. PCV21 does not contain certain serotypes that are included in other licensed pneumococcal vaccines but adds eight new serotypes. The Advisory Committee on Immunization Practices (ACIP) recommends use of a PCV for all adults aged ≥65 years, as well as adults aged 19-64 years with certain risk conditions for pneumococcal disease if they have not received a PCV or whose vaccination history is unknown. Previously, options included either 20-valent PCV (PCV20; Prevnar20; Wyeth Pharmaceuticals, Inc.) alone or a 15-valent PCV (PCV15; VAXNEUVANCE; Merck Sharp & Dohme, LLC) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23; Merck Sharp & Dohme, LLC). Additional recommendations for use of PCV20 exist for adults who started their pneumococcal vaccination series with 13-valent PCV (PCV13; Prevnar13; Wyeth Pharmaceuticals, Inc.). The ACIP Pneumococcal Vaccines Work Group employed the Evidence to Recommendations framework to guide its deliberations on PCV21 vaccination among U.S. adults. On June 27, 2024, ACIP recommended a single dose of PCV21 as an option for adults aged ≥19 years for whom PCV is currently recommended. Indications for PCV have not changed from previous recommendations. This report summarizes evidence considered for these recommendations and provides clinical guidance for use of PCV21.


Assuntos
Comitês Consultivos , Infecções Pneumocócicas , Vacinas Pneumocócicas , Vacinas Conjugadas , Humanos , Vacinas Pneumocócicas/administração & dosagem , Estados Unidos , Adulto , Pessoa de Meia-Idade , Idoso , Infecções Pneumocócicas/prevenção & controle , Vacinas Conjugadas/administração & dosagem , Adulto Jovem , Esquemas de Imunização , Centers for Disease Control and Prevention, U.S.
13.
Sci Rep ; 14(1): 21676, 2024 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289433

RESUMO

Although Jewish people in the US are often racialized (i.e., perceived by others) as White, Jewish Americans vary in the extent to which they consider themselves White, and in how strongly they identify with being Jewish. Based on prior findings that identifying with a White ethnic subgroup (e.g., Irish, Italian) can reduce prejudice toward racial and ethnic minorities, we predicted that strongly identified Jewish Americans would exhibit less intergroup bias than weakly identified Jewish Americans. For the present research, we recruited participants whose religious affiliation was Jewish but who self-identified as racially White. In a preregistered correlational study, Jewish identification was associated with lower bias, whereas White identification was associated with greater bias, toward Whites relative to racial/ethnic minorities. The relationship between Jewish identification and intergroup bias was accounted for by high Jewish identifiers' perceptions that they could personally contribute to diversity in groups and organizations. Across three meta-analyzed experiments, participants whose religious minority (Jewish) identity was made salient exhibited less intergroup bias than did control participants, and in one preregistered experiment, perceived personal contributions to diversity mediated the effect of condition on intergroup bias. Implications for the forms of ethnic identity that predict more versus less intergroup bias in an increasingly multicultural society are discussed.


Assuntos
Atitude , Judeus , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Diversidade Cultural , Judeus/psicologia , Preconceito/psicologia , Identificação Social , Estados Unidos , Brancos/psicologia
14.
Neurology ; 103(7): e209879, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39236269

RESUMO

Approaching patients with paraproteinemic neuropathies can be challenging for the practicing neurologist, and a well-defined strategy considering specific etiologies is necessary to arrive at the correct diagnosis. In this case, a 49-year-old man presented with a 2-year history of progressive upper then lower extremity numbness, weakness, gait instability, and tremors. His examination was marked by proximal and distal symmetric upper and lower extremity weakness, large more than small-fiber sensory loss, prominent sensory ataxia, action and postural tremors, and globally absent deep tendon reflexes. His workup was notable for a chronic demyelinating sensorimotor polyradiculoneuropathy and a monoclonal immunoglobulin (Ig) M kappa gammopathy. This case highlights the approach to a patient with a rare subtype of IgM paraproteinemic neuropathy with a review of the differential diagnoses, red flag features of co-occurring hematologic disorders, and guided workup. We further discuss typical features of this rare diagnosis and therapeutic options.


Assuntos
Raciocínio Clínico , Transtornos Neurológicos da Marcha , Hipestesia , Paraproteinemias , Tremor , Humanos , Masculino , Pessoa de Meia-Idade , Tremor/diagnóstico , Tremor/etiologia , Hipestesia/etiologia , Hipestesia/diagnóstico , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/diagnóstico , Paraproteinemias/complicações , Paraproteinemias/diagnóstico , Diagnóstico Diferencial
15.
Biomedicines ; 12(8)2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39200238

RESUMO

Spermatogenesis produces male gametes from spermatogonial stem cells (SSC), beginning at puberty. Modern-day laboratory techniques allow for the long-term culture of SSC and in vitro spermatogenesis. The specific biochemical processes that occur during spermatogenesis remain poorly understood. One particular element of spermatogenesis that has yet to be characterized is the role of microRNAs (miRNA), short, non-transcribed RNAs that act as post-translational regulators of gene activity. In this study, we seek to describe the presence of miRNA in a two-dimensional (2D) SSC culture and a 3D human testis organoid (HTO) system. Testicular cells were isolated from the frozen tissue of three brain-dead subjects, propagated in cultures for four to five weeks, and used to form 3D HTOs. Following organoid formation, differentiation of testicular cells was induced. RNA was isolated from the whole testis tissue (WT) showing in vivo conditions, HTO Day Zero (2D SSC culture), Day 2 HTOs, and Day 23 differentiated HTOs, then analyzed for changes in miRNA expression using the Nanostring nCounter miRNA panel. One hundred ninety-five miRNAs met the criteria for expression in WT, 186 in 2D culture, 190 in Day 2 HTOs, and 187 in differentiated HTOs. One hundred thirty-three miRNAs were common across all conditions, and 41, 17, 6, and 11 miRNAs were unique for WT, 2D culture, Day 2 HTOs, and differentiated HTOs, respectively. Twenty-two miRNAs were similar between WT and differentiated HTOS. We evaluated the miRNA expression profiles of progressively complex stages of testicular cell culture, culminating in a 3D organoid model capable of meiotic differentiation, and compared these to WT. We identified a great variance between the native tissue and the culture system; however, some miRNAs are preserved. These data may provide avenues for deeper understanding of spermatogenesis and the ability to improve this process in the laboratory. Research on miRNA continues to be an essential avenue for understanding human spermatogenesis.

16.
Sci Rep ; 14(1): 19474, 2024 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-39198514

RESUMO

Patients with high-grade glioma (HGG) have an extremely poor prognosis compounded by a lack of advancement in clinical care over the past few decades. Regardless of classification, most newly diagnosed patients receive the same treatment, radiation and temozolomide (RT/TMZ). We developed a functional precision oncology test that prospectively identifies individual patient's response to this treatment regimen. Tumor tissues isolated from patients with newly diagnosed HGG enrolled in 3D PREDICT REGISTRY were evaluated for response to chemotherapeutic agents using the 3D Predict™ Glioma test. Patients receiving RT/TMZ were followed for 2 years. Clinical outcomes including imaging, assessments, and biomarker measurements were compared to patient matched test-predicted therapy response. Median survival between test-predicted temozolomide responders and test-predicted temozolomide non-responders revealed a statistically significant increase in progression-free survival when using the test to predict response across multiple subgroups including HGG (5.8 months), glioblastoma (4.7 months), and MGMT unmethylated glioblastoma (4.7 months). Overall survival was also positively separated across the subgroups at 7.6, 5.1, and 6.3 months respectively. The strong correlation of 3D Predict Glioma test results with clinical outcomes demonstrates that this functional test is prognostic in patients treated with RT/TMZ and supports aligning clinical treatment to test-predicted response across varying HGG subgroups.


Assuntos
Neoplasias Encefálicas , Glioma , Temozolomida , Humanos , Temozolomida/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Glioma/mortalidade , Glioma/terapia , Glioma/patologia , Glioma/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/tratamento farmacológico , Adulto , Idoso , Prognóstico , Antineoplásicos Alquilantes/uso terapêutico , Resultado do Tratamento , Gradação de Tumores , Intervalo Livre de Progressão
17.
Neurophotonics ; 11(3): 035007, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39139631

RESUMO

Significance: Genetically encoded voltage indicators (GEVIs) are a valuable tool for studying neural circuits in vivo, but the relative merits and limitations of one-photon (1P) versus two-photon (2P) voltage imaging are not well characterized. Aim: We consider the optical and biophysical constraints particular to 1P and 2P voltage imaging and compare the imaging properties of commonly used GEVIs under 1P and 2P excitation. Approach: We measure the brightness and voltage sensitivity of voltage indicators from commonly used classes under 1P and 2P illumination. We also measure the decrease in fluorescence as a function of depth in the mouse brain. We develop a simple model of the number of measurable cells as a function of reporter properties, imaging parameters, and desired signal-to-noise ratio (SNR). We then discuss how the performance of voltage imaging would be affected by sensor improvements and by recently introduced advanced imaging modalities. Results: Compared with 1P excitation, 2P excitation requires ∼ 10 4 -fold more illumination power per cell to produce similar photon count rates. For voltage imaging with JEDI-2P in the mouse cortex with a target SNR of 10 (spike height to baseline shot noise), a measurement bandwidth of 1 kHz, a thermally limited laser power of 200 mW, and an imaging depth of > 300 µ m , 2P voltage imaging using an 80-MHz source can record from no more than ∼ 12 neurons simultaneously. Conclusions: Due to the stringent photon-count requirements of voltage imaging and the modest voltage sensitivity of existing reporters, 2P voltage imaging in vivo faces a stringent tradeoff between shot noise and tissue photodamage. 2P imaging of hundreds of neurons with high SNR at a depth of > 300 µ m will require either major improvements in 2P GEVIs or qualitatively new approaches to imaging.

18.
Open Forum Infect Dis ; 11(8): ofae419, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39113830

RESUMO

Among 98 participants with penile discharge symptoms of Chlamydia trachomatis or Neisseria gonorrhoeae at a walk-in sexual health clinic, 11 were diagnosed with Mycoplasma genitalium, 10 had antibiotic resistance, and 6 were incorrectly presumptively treated. Our findings highlight the importance of public health strategies and research to curb M genitalium.

20.
Emerg Med Australas ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39021286

RESUMO

OBJECTIVE: To profile the initial 6-month experience at the Victorian Heart Hospital (VHH) cardiac emergency (CE). The primary objective was to describe VHH CE patient characteristics, including presenting complaint, final diagnosis and disposition. Secondary objectives were to report on patient numbers, patient source and quality indicator performance including ambulance off-load by 40 min, waiting time and length of stay (LOS). METHODS: A retrospective review included all patients who presented to the VHH CE from 9 March 2023 to 8 September 2023. Patient reports containing the relevant clinical information were generated from the CE electronic medical record system. Diagnoses of MI were checked for accuracy by full record review. RESULTS: There were 3303 CE presentations in the first 6 months of operation, of which 6% were transferred from other sites. Median age was 65 years (interquartile range [IQR]: 53-77), 56% were males; the most common presenting complaints were presumed cardiac chest pain (67%) and arrhythmia (17%). The admission, discharge and transfer rates were 38%, 54% and 8%, respectively. In total, 15% were diagnosed with MI. The most common diagnoses for discharged and admitted patients were non-specific chest pain (57%) and ST-elevation MI (22%), respectively. Ambulance off-load by 40 min was met for 96%. Median waiting time was 6 min (IQR: 3-10). Median CE LOS for discharged and admitted patients was 3.2 h (IQR: 2.5-4.0) and 3.7 h (IQR: 1.8-6.0), with 75% and 56% being <4 h, respectively. CONCLUSIONS: The population predominantly had cardiovascular disease as expected. Some performance indicators, including ED LOS, were identified as requiring intervention.

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