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1.
Ecol Evol ; 14(5): e11254, 2024 May.
Article in English | MEDLINE | ID: mdl-38746545

ABSTRACT

Numerous genomic methods developed over the past two decades have enabled the discovery and extraction of orthologous loci to help resolve phylogenetic relationships across various taxa and scales. Genome skimming (or low-coverage genome sequencing) is a promising method to not only extract high-copy loci but also 100s to 1000s of phylogenetically informative nuclear loci (e.g., ultraconserved elements [UCEs] and exons) from contemporary and museum samples. The subphylum Anthozoa, including important ecosystem engineers (e.g., stony corals, black corals, anemones, and octocorals) in the marine environment, is in critical need of phylogenetic resolution and thus might benefit from a genome-skimming approach. We conducted genome skimming on 242 anthozoan corals collected from 1886 to 2022. Using existing target-capture baitsets, we bioinformatically obtained UCEs and exons from the genome-skimming data and incorporated them with data from previously published target-capture studies. The mean number of UCE and exon loci extracted from the genome skimming data was 1837 ± 662 SD for octocorals and 1379 ± 476 SD loci for hexacorals. Phylogenetic relationships were well resolved within each class. A mean of 1422 ± 720 loci was obtained from the historical specimens, with 1253 loci recovered from the oldest specimen collected in 1886. We also obtained partial to whole mitogenomes and nuclear rRNA genes from >95% of samples. Bioinformatically pulling UCEs, exons, mitochondrial genomes, and nuclear rRNA genes from genome skimming data is a viable and low-cost option for phylogenetic studies. This approach can be used to review and support taxonomic revisions and reconstruct evolutionary histories, including historical museum and type specimens.

2.
Int Nurs Rev ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38661539

ABSTRACT

AIMS: To describe the development process of a device from the conception of the idea to the first contact with the commercial environment, and to demonstrate its practical application through an interdisciplinary collaboration between nursing and engineering for the design of a protective device for peripheral venous catheters. BACKGROUND: Nurses are key agents for identifying unresolved needs or problems related to nursing care. To address these needs, creative ideation processes are often triggered among nurses to seek technological answers to these challenges. RESULTS: The ten steps to develop a device are presented: (1) detecting an unsatisfied clinical need; (2) searching for preexisting marketed products; (3) searching for patents; (4) maintaining confidentiality throughout the process; (5) obtaining institutional support; (6) forming a multidisciplinary team; (7) developing the idea; (8) applying for a patent; (9) building the prototype; (10) marketing the device. This methodology was applied to design a protective device for peripheral venous catheters in hospitalized patients. CONCLUSIONS: Nurses can play a key role in the promotion of healthcare innovation in their field to improve procedures, thanks to their direct contact with patients, and by providing their insight on devices that can enhance patient care. The successful interdisciplinary collaboration between nurses and engineers can provide a response to relevant clinical problems such as the manipulation or removal of peripheral venous catheters. IMPLICATIONS FOR NURSING AND/OR HEALTH POLICY: A hospital policy is required to encourage the participation of nurses in innovative actions. Furthermore, it is important to support nurse leaders who can play a pivotal role in incorporating creativity into work environments and empowering other nurses to innovatively address clinical issues. NO PATIENT OR PUBLIC CONTRIBUTION: This article describes the process for developing a health device.

3.
J Clin Med ; 13(8)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38673714

ABSTRACT

Background: The care of psoriatic patients requires a multidisciplinary approach that addresses not only skin involvement but also cardiovascular risk factors. Coordination between dermatology and internal medicine departments, with a specific focus on treatment and long-term follow-up, can substantially improve the course of a disease and its associated complications. Objective: to evaluate the effects of the holistic management of patients with psoriasis by a multidisciplinary team consisting of dermatology and internal medicine specialists. Methods: We conducted an observational, prospective, single-center case-control study between October 2016 and December 2019 in San Jorge University Hospital (Huesca, Spain). Cases included patients undergoing follow-up in the combined dermatology and internal medicine clinic. The control group consisted of an equivalent number of randomly selected, age- and sex-matched patients with moderate-to-severe psoriasis who were seen in the general dermatology department of the same hospital during the same time period. Main outcomes and measures: The primary outcome was the control of psoriatic disease and cardiovascular risk factors such as weight, blood pressure, waist circumference, body mass index (BMI), SCORE index (Systematic Coronary Risk Evaluation), and blood test parameters, as well as diet, physical exercise, and habits such as tobacco and alcohol consumption. To compare data collected over time, data were grouped into three time periods: baseline (t1), intermediate (t2), and final (t3). Results: The case group consisted of 27 patients, and the control group consisted of 25 patients. Multivariate analysis was used to evaluate the relationship between the 10-year risk of experiencing a cardiovascular event (SCORE) and the clinical characteristics and analytical variables of patients with psoriasis and controls (n = 52). The variables that were significantly associated with a higher 10-year risk of experiencing a cardiovascular event were age (OR, 1.33; CI95% 1.21-1.50; p < 0.001); smoking (OR, 5.05, CI95% 1.07-27.37; p = 0.047); PASI (OR, 7.98, CI95% 2.32-35.86; p = 0.003); BSA (OR, 1.22, CI95% 1.01-1.49; p = 0.044); and being a control patient (OR, 3.26; CI95% 0.84-13.56; p = 0.029). Conclusions: Pharmacological and behavioral interventions carried out as part of the procedure of the multidisciplinary clinic resulted in improvements in the following variables relative to the control group: PASI, BSA, DLQI, PSOLIFE, lipid profile, insulin and HOMA-IR GGT levels, vitamin D levels, and SCORE. These findings indicate the beneficial effect of the multidisciplinary clinic, which reduced the risk of cardiovascular events in psoriatic patients with metabolic comorbidities.

4.
Ophthalmol Ther ; 13(5): 1197-1210, 2024 May.
Article in English | MEDLINE | ID: mdl-38446281

ABSTRACT

INTRODUCTION: To evaluate the short-term efficacy of cyclosporine A (CsA)-0.1% cationic emulsion (CE) in patients with dry eye disease (DED) and mitigation of the inflammatory flares triggered by desiccating stress environments. METHODS: A single-center non-randomized clinical trial was performed at a tertiary care setting. Twenty patients with DED treated with CsA 0.1% CE were exposed to a normal controlled environment (NCE) (23 °C, 50% relative humidity) and an adverse controlled environment (ACE) (23 °C, 10% relative humidity, 0.43 m/s localized airflow) during baseline and the 1- and 3-month visits. Patients underwent the following evaluations: conjunctival hyperemia and staining, corneal fluorescein staining (CFS) using the Oxford and Cornea and Contact Lens Research Unit (CCLRU) scale, meibomian gland (MG) secretion quality, Dry Eye Questionnaire-5, Symptom Assessment in Dry Eye (SANDE II), and Change in Dry Eye Symptoms Questionnaire. Multivariate models were adjusted for statistical analysis. RESULTS: Nineteen women and one man (mean age, 58.9 ± 12.3 years) completed the study. All symptom questionnaires, CFS, conjunctival hyperemia and staining, and MG secretion quality improved (p ≤ 0.003) with 1 month of treatment; improvements were maintained after 3 months (p ≤ 0.02), except for SANDE II (p ≥ 0.07). The CFS worsening (total CCLRU) after baseline ACE exposure (from 8.6 to 10.1) was higher, although not significant (p = 0.64), compared with 1 month (from 5.4 to 5.8) and 3 months (from 5.0 to 5.9) after treatment. CONCLUSION: Topical CsA-0.1% CE improved DED signs and symptoms after 1 month of treatment under controlled environmental conditions. Future studies should confirm the benefit of CsA-0.1% CE in desiccating stress environments. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04492878.

5.
Exp Eye Res ; 241: 109854, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38453037

ABSTRACT

Mucosal chemokines have antimicrobial properties and play an important role in mucosal immunity. However, little is known about their expression on the ocular surface. This study aimed to analyze the expression of the mucosal chemokines CCL28, CXCL14 and CXCL17 in corneal and conjunctival epithelial cells under in vitro dry eye (DE) conditions, and in conjunctival samples from healthy subjects and DE patients. Human corneal epithelial cells (HCE) and immortalized human conjunctival epithelial cells (IM-HConEpiC) were incubated under hyperosmolar (400-500 mOsM) or inflammatory (TNF-α 25 ng/mL) conditions for 6 h and 24 h to measure CCL28, CXCL14, and CXCL17 gene expression by RT-PCR and their secretion by immunobead-based analysis (CCL28, CXCL14) and ELISA (CXCL17). Additionally, twenty-seven DE patients and 13 healthy subjects were included in this study. DE-related questionnaires (OSDI, mSIDEQ and NRS) evaluated symptomatology. Ocular surface integrity was assessed using vital staining. Tactile sensitivity was measured with Cochet-Bonnet esthesiometer, and mechanic and thermal (heat and cold) sensitivity using Belmonte's non-contact esthesiometer. Subbasal nerve plexus and dendritic cell density were analyzed by in vivo confocal microscopy. Conjunctival cells from participants were collected by impression cytology to measure mucosal chemokines gene expression by RT-PCR. Our results showed that HCE and IM-HConEpiC cells increased CCL28, CXCL14, and CXCL17 secretion under hyperosmolar conditions. The gene expression of CCL28 was significantly upregulated in conjunctival samples from DE patients. CCL28 expression correlated positively with symptomatology, corneal staining, heat sensitivity threshold, and dendritic cell density. CXCL14 expression correlated positively with age, ocular pain, conjunctival staining, tactile sensitivity, and image reflectivity. CXCL17 expression correlated positively with corneal staining. These results suggest that corneal and conjunctival epithelial cells could be a source of CCL28, CXCL14, and CXCL17 on the ocular surface and that CCL28 might be involved in DE pathogenesis.


Subject(s)
Dieldrin/analogs & derivatives , Dry Eye Syndromes , Humans , Dry Eye Syndromes/pathology , Chemokines/genetics , Cornea/pathology , Conjunctiva/pathology , Chemokines, CC , Chemokines, CXC
6.
Eur J Clin Microbiol Infect Dis ; 43(5): 999-1002, 2024 May.
Article in English | MEDLINE | ID: mdl-38376633

ABSTRACT

This case report details the management of a 79-year-old male with recurrent methicillin-resistant Staphylococcus capitis bacteremia and endocarditis. The patient's clinical journey encompassed multiple hospital admissions, with challenges in managing endocarditis, pacemaker replacements, and potential cutaneous sources of infection. The treatment regimen included intravenous antibiotic therapy during hospitalization and suppressive antibiotic treatment upon discharge, alongside a decolonization strategy for his scalp lesions.


Subject(s)
Anti-Bacterial Agents , Bacteremia , Endocarditis, Bacterial , Staphylococcus capitis , Humans , Male , Aged , Bacteremia/drug therapy , Bacteremia/microbiology , Anti-Bacterial Agents/therapeutic use , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/diagnosis , Staphylococcus capitis/drug effects , Staphylococcus capitis/isolation & purification , Staphylococcus capitis/genetics , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcal Infections/diagnosis , Recurrence
7.
Nutr. hosp ; 41(1): 244-248, Ene-Feb, 2024. tab
Article in Spanish | IBECS | ID: ibc-230904

ABSTRACT

El presente documento tiene como objetivo plantear y justificar la incorporación del dietista-nutricionista en los equipos multidisciplinares deatención integrada en la educación, el tratamiento y el seguimiento de aquellos pacientes con patologías que cursen con alteraciones del estadonutricional, tanto en su defecto como en su exceso, en el área sanitaria de la Comunidad Autónoma de Madrid.El estado nutricional de los pacientes hospitalizados se beneficiará de la incorporación del dietista-nutricionista al equipo multidisciplinar que,actualmente, se ocupa de la atención de estos. El manejo de la terapia nutricional por dietistas-nutricionistas ha demostrado ser costo-efectiva,habida cuenta de la repercusión sanitaria que tiene el estado nutricional en la evolución clínica y prevención de enfermedades como la diabetes,los trastornos de la conducta alimentaria, la obesidad, el cáncer, la insuficiencia cardiaca, la osteoporosis, la enfermedad celiaca y la enfermedadrenal crónica, entre otras.(AU)


The present document has the objective of justifying the incorporation of a dietician/nutritionist to the multidisciplinary teams of specialized carethat provide education, food anamnesis, nutritional recommendations, treatment and follow up of those patients in risk of malnutrition in Madrid.The appropriate nutritional status of hospitalized patients bears a close relationship with the existence of dieticians at hospitals. Dieticians usenutrition therapy as a cost-effective means to achieve significant health benefits by preventing or altering the course of diabetes, obesity, hyper-tension, lipid metabolism disorders, heart failure, osteoporosis, celiac disease, and chronic kidney disease, among other diseases.(AU)


Subject(s)
Humans , Male , Female , Nutritionists , Personnel Selection , Patients , Nutritional Status , Nutrition Therapy , Spain , Hospitals, Public , Malnutrition , Mass Screening
8.
Nutr Hosp ; 41(1): 244-248, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38224303

ABSTRACT

Introduction: The present document has the objective of justifying the incorporation of a dietician/nutritionist to the multidisciplinary teams of specialized care that provide education, food anamnesis, nutritional recommendations, treatment and follow up of those patients in risk of malnutrition in Madrid. The appropriate nutritional status of hospitalized patients bears a close relationship with the existence of dieticians at hospitals. Dieticians use nutrition therapy as a cost-effective means to achieve significant health benefits by preventing or altering the course of diabetes, obesity, hypertension, lipid metabolism disorders, heart failure, osteoporosis, celiac disease, and chronic kidney disease, among other diseases.


Introducción: El presente documento tiene como objetivo plantear y justificar la incorporación del dietista-nutricionista en los equipos multidisciplinares de atención integrada en la educación, el tratamiento y el seguimiento de aquellos pacientes con patologías que cursen con alteraciones del estado nutricional, tanto en su defecto como en su exceso, en el área sanitaria de la Comunidad Autónoma de Madrid. El estado nutricional de los pacientes hospitalizados se beneficiará de la incorporación del dietista-nutricionista al equipo multidisciplinar que, actualmente, se ocupa de la atención de estos. El manejo de la terapia nutricional por dietistas-nutricionistas ha demostrado ser costo-efectiva, habida cuenta de la repercusión sanitaria que tiene el estado nutricional en la evolución clínica y prevención de enfermedades como la diabetes, los trastornos de la conducta alimentaria, la obesidad, el cáncer, la insuficiencia cardiaca, la osteoporosis, la enfermedad celiaca y la enfermedad renal crónica, entre otras.


Subject(s)
Malnutrition , Nutritionists , Humans , Nutritional Status , Hospitals, University , Malnutrition/therapy , Nutritional Support
9.
Cont Lens Anterior Eye ; 47(1): 102096, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38097423

ABSTRACT

PURPOSE: This study aimed to assess the subjective and objective differences among the steps of the contact lens discomfort (CLD) progression classification established by the Tear Film & Ocular Surface Society (TFOS) using questionnaires and clinical signs, and to propose a simplified classification. METHODS: Contact lens (CL) wearers were evaluated in a single visit. The Contact Lens Dry Eye Questionnaire (CLDEQ)-8, the Contact Lens Discomfort Index, and Visual Analog Scales for discomfort and dryness were administered. The non-invasive break-up time, the tear film lipid layer thickness, conjunctival hyperaemia and papillae, lid-parallel conjunctival folds, the fluorescein tear film break-up time, corneal and conjunctival staining, lid wiper epitheliopathy, and the Schirmer test were assessed. Sign and symptom scores were compared among TFOS CLD progression steps using analysis of variance or the Kruskal-Wallis H test. Steps 1 and 2 (reduced comfort), and steps 3 and 4 (reduced wearing time) of the TFOS classification were combined to obtain a simplified classification, and the same comparison was performed. A p-value ≤ 0.05 was considered statistically significant. RESULTS: One hundred-fifty CL wearers (97 women and 53 men) aged 34.4 ± 12.6 years were included. In the TFOS classification, there were significant differences between step 0 (no CLD) and the rest of the severity steps for the scores obtained in all questionnaires (p ≤ 0.015). All steps were differentiated (p ≤ 0.032) based on the simplified classification for all questionnaires, except steps 1 and 2 for the CLDEQ-8 and dryness VAS (p = 0.089 and p = 0.051, respectively). There were no differences (all p ≥ 0.06) between the sign scores among the steps of either classification. CONCLUSION: CLD management is encouraged from its first appearance. Simplifying the phases of CLD severity may allow a more accurate classification and a better awareness of the problem by clinicians and CL wearers by using more straightforward simple messages.


Subject(s)
Contact Lenses, Hydrophilic , Dry Eye Syndromes , Male , Humans , Female , Contact Lenses, Hydrophilic/adverse effects , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/etiology , Conjunctiva , Cornea , Tears
10.
Ophthalmic Physiol Opt ; 44(1): 124-130, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37974449

ABSTRACT

PURPOSE: To assess the reliability and agreement of non-invasive break-up time (NIBUT) in symptomatic and asymptomatic contact lens (CL) wearers using automatic objective and conventional subjective techniques. METHODS: In this prospective cross-sectional study, soft CL wearers, classified into symptomatic and asymptomatic based on the Contact Lens Dry Eye Questionnaire-8, underwent NIBUT assessment with the CL in situ. The CA-800 Corneal Analyzer and the EasyTear® VIEW+ Tearscope were used for objective and subjective evaluation, respectively. The within-subject repeatability and intraclass correlation coefficient (ICC) were calculated. The agreement between the devices was compared using the Bland-Altman method. RESULTS: A total of 141 CL wearers (51 male and 90 female) with a mean age of 33.6 (SD = 12.2) years were included. The repeatability and ICC values obtained with the CA-800 device when measuring NIBUT were 5.4 s and 58.6% across the whole sample, 4.2 s and 48.8% for the asymptomatic group and 7.1 s and 68.4% for the symptomatic group. When using the subjective method (EasyTear®), the respective repeatability and ICC values were 7.3 s and 32.7% for the whole sample, 6.5 s and 30.4% for the asymptomatic group and 8.6 s and 35.9% for the symptomatic group. The CA-800 device provided significantly (p < 0.001) shorter NIBUT values compared with EasyTear® for the whole sample (3.3 [2.9] vs. 8.1 [3.4] s), the asymptomatic (3.3 [3.0] vs. 7.7 [3.6] s) and the symptomatic (3.8 [2.9] vs. 8.6 [3.0] s) groups. CONCLUSION: Objective (CA-800) NIBUT assessment provides more reliable measurements than the conventional subjective technique using the EasyTear® device. However, CL practitioners should also be aware that the objective method indicates shorter NIBUT values. Symptomatic CL wearers may also need a higher number of NIBUT measurements to obtain reliable estimations.


Subject(s)
Contact Lenses, Hydrophilic , Dry Eye Syndromes , Humans , Male , Female , Adult , Prospective Studies , Reproducibility of Results , Cross-Sectional Studies , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/etiology , Tears
11.
Ocul Surf ; 31: 31-42, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38128761

ABSTRACT

PURPOSE: This study aimed to analyze the differences in the expression of pain-related genes in conjunctival epithelial cells among symptomatic contact lens (CL) wearers (SCLWs), asymptomatic CL wearers (ACLWs), and non-CL wearers (non-CLWs). METHODS: For this study, 60 participants (20 non-CLWs, 40 CLWs) were enrolled. The CLW group comprised 20 ACLWs and 20 SCLWs according to the Contact Lens Dry Eye Questionnaire short form©. Conjunctival cells were collected using impression cytology, and RNA was isolated and used to determine the expression levels of 85 human genes involved in neuropathic and inflammatory pain. The effects of CL wear and discomfort were evaluated using mixed-effects ANOVA with partially nested fixed-effects model. Gene set enrichment analysis was performed to assign biological meaning to sets of differentially expressed genes. RESULTS: Six genes (CD200, EDN1, GRIN1, PTGS1, P2RX7, and TNF) were significantly upregulated in CLWs compared to non-CLWs. Eleven genes (ADORA1, BDKRB1, CACNA1B, DBH, GRIN1, GRM1, HTR1A, PDYN, PTGS1, P2RX3, and TNF) were downregulated in SCLWs compared to ACLWs. These genes were mainly related to pain, synaptic transmission and signaling, ion transport, calcium transport and concentration, and cell-cell signaling. CONCLUSIONS: CL wear modified the expression of pain- and inflammation-related genes in conjunctival epithelial cells. These changes may be in part, along with other mechanisms, responsible for CL discomfort in SCLWs.


Subject(s)
Contact Lenses, Hydrophilic , Dry Eye Syndromes , Humans , Conjunctiva/metabolism , Epithelial Cells/metabolism , Dry Eye Syndromes/metabolism , Pain , Gene Expression
12.
Adv Ther ; 41(2): 696-715, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38110653

ABSTRACT

INTRODUCTION: Teclistamab is the first approved B cell maturation antigen × CD3 bispecific antibody with precision dosing for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). We compared the effectiveness of teclistamab in MajesTEC-1 versus real-world physician's choice of therapy (RWPC) in patients from the prospective, non-interventional LocoMMotion and MoMMent studies. METHODS: Patients treated with teclistamab from MajesTEC-1 (N = 165) were compared with an external control arm from LocoMMotion (N = 248) or LocoMMotion + MoMMent pooled (N = 302). Inverse probability of treatment weighting adjusted for imbalances in prognostic baseline characteristics. The relative effect of teclistamab versus RWPC for overall response rate (ORR), very good partial response or better (≥ VGPR) rate, and complete response or better (≥ CR) rate was estimated with an odds ratio using weighted logistic regression transformed into a response-rate ratio (RR) and 95% confidence interval (CI). Weighted proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Baseline characteristics were well balanced between treatment cohorts after reweighting. Patients treated with teclistamab had significantly improved outcomes versus RWPC in LocoMMotion: ORR (RR [95% CI], 2.44 [1.79-3.33]; p < 0.0001), ≥ VGPR (RR 5.78 [3.74-8.93]; p < 0.0001), ≥ CR (RR 113.73 [15.68-825.13]; p < 0.0001), DOR (HR 0.39 [0.24-0.64]; p = 0.0002), PFS (HR 0.48 [0.35-0.64]; p < 0.0001), and OS (HR 0.64 [0.46-0.88]; p = 0.0055). Teclistamab versus RWPC in LocoMMotion + MoMMent also had significantly improved outcomes: ORR (RR 2.41 [1.80-3.23]; p < 0.0001), ≥ VGPR (RR 5.91 [3.93-8.88]; p < 0.0001), ≥ CR (RR 132.32 [19.06-918.47]; p < 0.0001), DOR (HR 0.43 [0.26-0.71]; p = 0.0011), PFS (HR 0.49 [0.37-0.66]; p < 0.0001), and OS (HR 0.69 [0.50-0.95]; p = 0.0247). CONCLUSION: Teclistamab demonstrated significantly improved effectiveness over RWPC in LocoMMotion ± MoMMent, emphasizing its clinical benefit as a highly effective treatment for patients with TCE RRMM. TRIAL REGISTRATION: MajesTEC-1, ClinicalTrials.gov NCT03145181 (phase 1) and NCT04557098 (phase 2); LocoMMotion, ClinicalTrials.gov NCT04035226; MoMMent, ClinicalTrials.gov NCT05160584.


Subject(s)
Antineoplastic Agents , Multiple Myeloma , Physicians , Humans , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Multiple Myeloma/drug therapy , Prospective Studies , Treatment Outcome , Comparative Effectiveness Research
13.
Nat Commun ; 14(1): 5825, 2023 09 20.
Article in English | MEDLINE | ID: mdl-37730678

ABSTRACT

Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults (n = 4) and patients with precursor (n = 8) and full-blown MM (n = 10). Large T cell clones from patients with MM expressed multiple immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting of PD-1 + LAG3 or PD-1 + TIGIT partially restored their function in mice with MM. We identify phenotypic hallmarks of large intratumoral T cell clones, and demonstrate that the CD27- and CD27+ T cell ratio, measured by flow cytometry, may serve as a surrogate of clonal T cell expansions and an independent prognostic factor in 543 patients with MM treated with lenalidomide-based treatment combinations.


Subject(s)
Multiple Myeloma , Adult , Humans , Animals , Mice , Multiple Myeloma/drug therapy , Multiple Myeloma/genetics , T-Lymphocytes , Programmed Cell Death 1 Receptor/genetics , Lenalidomide , Clone Cells
14.
Accid Anal Prev ; 193: 107293, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37738846

ABSTRACT

Vehicle occupants expect greater postural flexibility with the introduction of highly automated vehicles, such as reclined postures. Experiments have been conducted with post mortem human subjects to study the risk of injury under impact conditions in reclined postures. However, the influence of the pre-crash phase on the kinematics in reclined postures has not yet been thoroughly studied. The aim of the present study is to investigate human responses under low g braking conditions focusing on different backrest angles in a generic sled environment. Three 50th percentile male volunteers were recruited to participate in a sled experiment. Each of them was subjected to a total of fourteen trials under a braking pulse with a maximum acceleration of 0.7 g for 700 ms. Different sitting postures were investigated: from 23° to 45°, 60° and 75° backrest tilt with respect to the vertical axis. In addition, two different seat pan tilt angles were considered: a 16° tilt angle for 23°, 45° and 60° backrest inclination and a 36° tilt angle for 60° and 75° backrest inclination. Measurements of volunteer kinematics, muscle activation and interaction forces between the volunteers and the sled, among others, were acquired. Initial results show a significant reduction in maximum forward head displacement from the upright to the reclined postures (p < 0.02), with the exception of the 45° reclined posture. However, no significant difference in maximum head displacement was found between the different reclined postures (p > 0.1). Seat pan tilt angle did significantly influence forward head excursion when considering the same seatback inclination (p < 0.01). It is of great importance to investigate occupant kinematics during the pre-crash phase to understand its influence on the potential injuries that may occur with a reclined posture in the event of a collision.

15.
Zookeys ; 1173: 97-110, 2023.
Article in English | MEDLINE | ID: mdl-37577152

ABSTRACT

Black corals (Anthozoa: Antipatharia) are an anthozoan lineage in the class Hexacorallia that occur across a wide range of habitats from the tropics to the poles and from surface waters to depths deeper than 8000 m. A new species of black coral, Aphanipathespuertoricoensissp. nov., collected with a remotely operated vehicle 357 m deep off Puerto Rico is recognized in the family Aphanipathidae. The new species is characterized by very long and loosely coiled primary branches and up to 0.5 mm tall spines with as many as 40 or more small conical tubercles. A phylogeny composed of 13 taxa that are closely related to the new species was reconstructed from 793 nuclear loci to show their systematic relationships. Our study integrated morphological and genomic data to show that this new species is distinct from other species in the genus Aphanipathes. Furthermore, our results add to the growing knowledge of black coral diversity, while further demonstrating the need for exploration in deep waters of the Caribbean Sea.

16.
Res Gerontol Nurs ; 16(6): 283-290, 2023.
Article in English | MEDLINE | ID: mdl-37616481

ABSTRACT

People with dementia (PWD) have a higher risk of hospitalization than people without dementia. Hospitalizations are stressful events for PWD and their caregivers, representing a considerable change to their routines. The current descriptive longitudinal study aimed to identify the positive and negative reactions, experiences related to health and social integrated care, resource use, and work status of family caregivers of PWD or cognitive impairment admitted to the hospital with a proximal femur fracture undergoing surgery. Findings indicated that family caregivers (N = 174) are fully committed to providing assistance in activities of daily living and supervision, showing positive attitudes on self-esteem and negative attitudes toward lack of family support and impact on finances, schedule, and health. Overall caregiver experiences with integrated health and social care improved after hospitalization but decreased after discharge. One month after hospitalization, family caregivers maintained the same work hours but used fewer health care resources. Hospitalization represents a good opportunity to approach family caregivers and determine their needs to provide them with interventions to minimize their burden and improve their well-being. [Research in Gerontological Nursing, 16(6), 283-290.].


Subject(s)
Cognitive Dysfunction , Dementia , Humans , Caregivers/psychology , Activities of Daily Living , Longitudinal Studies , Hospitalization
17.
Adv Mater ; 35(36): e2211352, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37435994

ABSTRACT

The advent of immunotherapies with biological drugs has revolutionized the treatment of cancers and auto-immune diseases. However, in some patients, the production of anti-drug antibodies (ADAs) hampers the drug efficacy. The concentration of ADAs is typically in the range of 1-10 pm; hence their immunodetection is challenging. ADAs toward Infliximab (IFX), a drug used to treat rheumatoid arthritis and other auto-immune diseases, are focussed. An ambipolar electrolyte-gated transistor (EGT) immunosensor is reported based on a reduced graphene oxide (rGO) channel and IFX bound to the gate electrode as the specific probe. The rGO-EGTs are easy to fabricate and exhibit low voltage operations (≤ 0.3 V), a robust response within 15 min, and ultra-high sensitivity (10 am limit of detection). A multiparametric analysis of the whole rGO-EGT transfer curves based on the type-I generalized extreme value distribution is proposed. It is demonstrated that it allows to selectively quantify ADAs also in the co-presence of its antagonist tumor necrosis factor alpha (TNF-α), the natural circulating target of IFX.


Subject(s)
Biosensing Techniques , Humans , Immunoassay , Antibodies , Infliximab , Electrolytes
18.
Clin Kidney J ; 16(6): 1022-1034, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37260993

ABSTRACT

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. Methods: This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results: Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63-17.21]} and female sex [OR 2.46 (CI 1.19-5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [-2.22 kg (95% CI -2.79 to -1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [-0.36% (95% CI -0.51 to -0.21)], serum uric acid [-0.44 mg/dl (95% CI -0.60 to -0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11-0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28-0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions: SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.

20.
Clin Biomech (Bristol, Avon) ; 105: 105952, 2023 05.
Article in English | MEDLINE | ID: mdl-37187012

ABSTRACT

BACKGROUND: A deep understanding of human reactions and stabilization strategies is required to predict their kinematics under external dynamic loadings, such as those that occur in vehicle passengers. Low-level frontal accelerations have been thoroughly investigated; however, the human response to different lateral accelerations is not well understood. The objective of this study is to gain insight regarding the responses of seated humans to lateral perturbations from volunteer experiments in different configurations. METHODS: Five volunteers anthropometrically comparable to the 50th-percentile American male, were seated on a sled and submitted to 21 lateral pulses. Seven configurations, each repeated three times, were investigated in this study: a relaxed muscular condition with four pulses, namely, sine and plateau pulses of 0.1 and 0.3 g in a straight spinal posture; a relaxed muscular condition with a plateau pulse of 0.3 g in a sagging spinal posture; and a braced condition with both plateau pulses in a straight spinal posture. Upper body segment kinematics were assessed using inertial measurement units. FINDINGS: The maximum lateral bending of the head was found to differ significantly among the four acceleration pulses (p < 0.001). Braced muscles significantly reduced lateral bending compared to relaxed muscles (p < 0.001). However, no significant difference was found in lateral bending between straight and sagging spinal postures (p = 0.23). INTERPRETATION: The study shows that not only pulse amplitude but also pulse shape influences human responses to low accelerations, while spinal posture does not influence lateral head bending. These data can be used to evaluate numerical active human body models.


Subject(s)
Acceleration , Human Body , Humans , Male , Muscles , Biomechanical Phenomena/physiology , Head
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