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1.
Hand (N Y) ; : 15589447231222320, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240269

RESUMO

Carpal tunnel syndrome (CTS) is a debilitating condition that can cause significant morbidity. Corticosteroid injection (CI) is a popular treatment for CTS. Short-term benefits of CI for CTS have been reported, but there is little evidence on long-term outcomes. We performed a systematic review in the PubMed/MEDLINE and Cochrane Library databases to identify studies which reported outcomes of CI for CTS with at least 1-year follow-up. We identified 20 total studies and extracted data on outcomes such as number of patients needing eventual surgery or reinjection, complications, and functional scores. In included studies, 41.6% of patients underwent eventual carpal tunnel release surgery (CTRS), 29% underwent reinjection, there were no major and approximately 34/1133 (3.0%) minor complications, and median/mean time from CI to eventual CTRS ranged from 128 to 446 days. There was disparity on the long-term efficacy of CI for functional outcomes. The evidence indicates that CI is a very low risk procedure that has potential to improve symptoms enough to either prevent or, in most cases, delay the need for further reintervention. However, our conclusions are limited by the heterogeneity of available studies. There is a need for further, high-quality research on this topic.

2.
JBJS Rev ; 12(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38181103

RESUMO

¼ Orthopaedic surgeons are increasingly likely to encounter patients with obesity and/or type 2 diabetes taking glucagon-like peptide-1 (GLP-1) agonists for weight loss.¼ GLP-1 agonists are an effective treatment for weight loss with semaglutide and tirzepatide being the most effective agents. Randomized controlled trials using these agents have reported weight loss up to 21 kg (46 lb).¼ The use of GLP-1 agonists preoperatively can improve glycemic control, which can potentially reduce the risk of postoperative complications. However, multiple cases of intraoperative aspiration/regurgitation have been reported, potentially related to the effect of GLP-1 agonists on gastric emptying.¼ While efficacious, GLP-1 agonists may not produce sufficient weight loss to achieve body mass index cutoffs for total joint arthroplasty depending on individual patient factors, including starting bodyweight. Multifactorial approaches to weight loss with focus on lifestyle modification in addition to GLP-1 agonists should be considered in such patients.¼ Although GLP-1 agonists are efficacious agents for weight loss, they may not be accessible or affordable for all patients. Each patient's unique circumstances should be considered when creating an ideal weight loss plan during optimization efforts.


Assuntos
Diabetes Mellitus Tipo 2 , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Cirurgiões Ortopédicos , Humanos , Artroplastia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Redução de Peso , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/uso terapêutico
4.
World J Surg ; 47(10): 2474-2478, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37488333

RESUMO

OBJECTIVE: Transoral approaches in surgery are gaining global popularity. Transoral endoscopic and robotic thyroidectomies are well established due to the benefit of being truly scarless. Thyroid chondrolaryngoplasty reduces protrusion of the thyroid notch in transgender patients. The Sistrunk operation involves removal of the thyroglossal cyst and the central portion of the hyoid bone. In this cadaveric study, we developed a transoral thyroidectomy approach and assessed the feasibility of applying this technique to thyroid chondrolaryngoplasty and Sistrunk operation with the proper usage of a special endoscopic burr. METHODS: We performed surgery using the transoral vestibular approach with 13 fresh-frozen human cadavers. Unlike transoral thyroid surgery, which requires high-resolution detailed anatomical view, this technique uses a 5-mm 30-degree endoscope with a 5-mm central port. A smaller central port can reduce the risk of mental nerve paresthesia. A special endoscopic burr for functional endoscopic sinus surgery is used to thin the thyroid notch cartilage and cut the central portion of the hyoid bone. RESULTS: We successfully performed transoral thyroid chondrolaryngoplasty and transoral Sistrunk operation in 13 cadavers. CONCLUSION: Transoral chondrolaryngoplasty and transoral Sistrunk operation are feasible for transgender or thyroglossal cyst patients. It offers the additional benefit of being a scarless surgery and could play a promising role in minimally invasive thyroid surgeries. Proper use of an endoscopic drilling burr to thin thyroid notch cartilage and cutting the central portion of the hyoid bone can make transoral thyroid chondrolaryngoplasty and transoral Sistrunk operation safe and feasible .


Assuntos
Cirurgia Endoscópica por Orifício Natural , Cisto Tireoglosso , Humanos , Tireoidectomia/métodos , Glândula Tireoide/cirurgia , Cisto Tireoglosso/cirurgia , Endoscopia/métodos , Cadáver , Cirurgia Endoscópica por Orifício Natural/métodos
5.
Eur J Med Chem ; 259: 115668, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37490800

RESUMO

The taxane class of microtubule stabilizers are some of the most effective and widely used chemotherapeutics. The anticancer activity of taxanes arises from their ability to induce tubulin assembly by selectively recognizing the curved (c-) conformation in unassembled tubulin as compared to the straight (s-) conformation in assembled tubulin. We first designed and synthesized a series of 3'N-modified taxanes bearing covalent groups. Instead of discovering covalent taxanes, we found a series of non-covalent taxanes 2, in which the 3'N side chain was found to be essential for cytotoxicity due to its role in locking tubulin in the s-conformation. A representative compound bearing an acrylamide moiety (2h) exhibited increased binding affinity to the unassembled tubulin c-conformation and less cytotoxicity than paclitaxel. Further exploration of chemical space around 2h afforded a new series 3, in which derivatives such as 3l bind more tightly to both the s- and c-conformations of tubulin compared to paclitaxel, leading to more efficient promotion of tubulin polymerization and a greater persistence of in vitro efficacy against breast cancer cells after drug washout. Although 3l also had improved in vivo potency as compared to paclitaxel, it was also associated with increased systemic toxicity that required localized, intratumoral injection to observe potent and prolonged antitumor efficacy.


Assuntos
Paclitaxel , Tubulina (Proteína) , Tubulina (Proteína)/metabolismo , Paclitaxel/farmacologia , Paclitaxel/química , Taxoides/farmacologia , Taxoides/química , Microtúbulos
6.
PLoS One ; 18(7): e0289039, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37494379

RESUMO

Individuals with sickle cell disease are increasingly surviving into adulthood, many of whom have interest in future biological parenthood. Reproductive health knowledge is low among adolescent and young adult males and their caregivers. Their understanding of these topics is needed to optimize their reproductive health outcomes. As such, through collaboration with a community advisory board (adolescents and young adults with sickle cell disease and mothers of adolescent and young adult males with sickle cell disease) and digital design team, we developed a web-based sickle cell disease-focused reproductive health program entitled FUTURES to address these knowledge gaps. For phase I of this two phase feasibility and acceptability study, adolescent and young adult males and their caregivers will complete a pre- and post-program reproductive health knowledge and attitudes questionnaire to assess change in knowledge. In phase II, after learning about fertility testing as part of the FUTURES curriculum, adolescent and young adult male participants are given the option to pursue testing. The two-phase study aims to: 1) develop and test the feasibility, acceptability, and efficacy of a reproductive health web-based educational program at increasing reproductive health knowledge in male adolescent and young adult males with sickle cell disease and their caregivers, and 2) assess feasibility of fertility testing. The long-term goal is to improve reproductive and psychosocial outcomes among adolescent and young adult males with sickle cell disease.


Assuntos
Anemia Falciforme , Saúde Reprodutiva , Feminino , Humanos , Masculino , Adolescente , Adulto Jovem , Saúde Reprodutiva/educação , Reprodução , Mães , Internet
7.
Nat Commun ; 14(1): 1394, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36914633

RESUMO

Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase that plays an oncogenic role in breast, gastric and other solid tumors. However, anti-HER2 therapies are only currently approved for the treatment of breast and gastric/gastric esophageal junction cancers and treatment resistance remains a problem. Here, we engineer an anti-HER2 IgG1 bispecific, biparatopic antibody (Ab), zanidatamab, with unique and enhanced functionalities compared to both trastuzumab and the combination of trastuzumab plus pertuzumab (tras + pert). Zanidatamab binds adjacent HER2 molecules in trans and initiates distinct HER2 reorganization, as shown by polarized cell surface HER2 caps and large HER2 clusters, not observed with trastuzumab or tras + pert. Moreover, zanidatamab, but not trastuzumab nor tras + pert, elicit potent complement-dependent cytotoxicity (CDC) against high HER2-expressing tumor cells in vitro. Zanidatamab also mediates HER2 internalization and downregulation, inhibition of both cell signaling and tumor growth, antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP), and also shows superior in vivo antitumor activity compared to tras + pert in a HER2-expressing xenograft model. Collectively, we show that zanidatamab has multiple and distinct mechanisms of action derived from the structural effects of biparatopic HER2 engagement.


Assuntos
Anticorpos Biespecíficos , Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Receptor ErbB-2/metabolismo , Citotoxicidade Celular Dependente de Anticorpos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico
8.
J Hand Surg Glob Online ; 5(2): 215-218, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36974295

RESUMO

Rupture is a major concern after primary flexor tendon repair. The predominant treatment for rupture of the primary repair is immediate surgical exploration and repeat repair. However, repeat repair is challenging, including achieving ideal tension in the flexor mechanism. Further, immediate repeat repair is associated with poor outcomes, particularly in the small finger. As such, there is a need to improve both the technique and outcomes of repeat repair of primary flexor tendon rupture. We present a case of primary flexor tendon repair rupture treated with a novel combination of fractional tendon lengthening and the wide awake, local anesthesia, no tourniquet technique. A combination of these techniques has multiple benefits. An intraoperative, dynamic assessment of the digits enables immediate optimization of the repair. Further, these techniques allow for better intraoperative patient education and communication, increasing the likelihood of adherence to postoperative therapy and better overall outcomes.

9.
Plast Reconstr Surg ; 151(4): 673e-678e, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36729778

RESUMO

SUMMARY: The goal of wound reconstruction is the approximation of soft tissue and re-establishment of an acceptable appearance with minimal risk of complications. For large wound closure in the extremities, skin graft and flap reconstruction are common treatments but are associated with a variety of complications. Comparatively, tissue expansion can provide the opportunity to reconstruct large wounds with native, durable, and sensate tissue without significant donor site morbidity. External tissue expansion is less invasive and avoids complications associated with internal expansion. The authors treated 11 patients with varying extremity wound types and sizes with an external tissue expansion device. Patient age ranged from 18 to 68 years with an average age of 43.7 years (SD, ± 13.1 years). Average wound surface area was approximately 235 cm 2 (SD, ± 135.3 cm 2 ). Devices were affixed and left for 7 to 11 days before closure of the wounds. Outcomes were assessed at 2 to 36 weeks postoperative follow-up. All wounds were fully closed after treatment without need for secondary reconstructive procedures. No patient experienced major complications. All patients demonstrated intact sensation within the area of reconstruction equivalent to surrounding tissues. External tissue expansion, an excellent treatment option in extremity reconstruction, is efficacious and associated with lower complication rates compared with internal tissue expansion, skin grafts, and flap reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Doenças Musculoesqueléticas , Lesões dos Tecidos Moles , Humanos , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Estudos Retrospectivos , Retalhos Cirúrgicos/transplante , Expansão de Tecido , Transplante de Pele , Lesões dos Tecidos Moles/cirurgia , Extremidades/cirurgia , Doenças Musculoesqueléticas/cirurgia
10.
SN Comput Sci ; 4(2): 202, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36789247

RESUMO

Introduction: The study aims to present the potential benefits and challenges of incorporating communication technology (CT), namely synchronous computer-mediated communication (SCMC) (e.g., Zoom Video Communications), computer-mediated communication (CMC) (e.g., WhatsApp), and social networking sites (SNS) (e.g., Instagram) into the tertiary classroom based on the honest account of four English as a Second Language (ESL) teachers during the pandemic. The authors intend to explore the efficacy of SCMC in lowering language anxiety and in fostering closer teacher-student relationship as suggested by the previous literature (Abraham in Comput Assist Lang Learn 21:199-226, 2008; Aristika and Juandi in Emerg Sci J 5:443-456, 2021; Darhower in Synchronous computer-mediated communication in the intermediate foreign language class: a sociocultural case study, University of Pittsburgh, 2000; Hagenauer and Volet in Oxf Rev Educ 40:370-388, 2014). Method: Qualitative data collected from the authors' teaching reflections over a 13-week period were analyzed from a third-person perspective. The above collaborative autoethnography (CAE) approach was adopted in face of the then difficulties in data collection given factors such as social-distancing during the pandemic. The authors selected and agreed on the key observations, feelings, and anecdotes worth-examining in their first-time online teaching experience at informal group interviews facilitated by SCMC. Findings: It was identified by the authors that learners' text-based production in the target language increased possibly due to the novelty of online learning platforms, lower affective variables, and a closer teacher-student relationship fostered by teachers' increased self-disclosure and the reduced formality in communication technology. Despite the above potential benefits of CT in ESL, challenges, such as an increasingly blurred teacher-student professional distance, students' increased code-mixed production in their L1 and L2, and the resultant 'teacher burnout' due to the obscured concept of standard office hours, were observed. The incorporation of CT into English Language Teaching (ELT) is desirable for its potential benefits in the affective domain of both teachers and students. However, it is recommended that teachers should establish guidelines in the use of CMC and SNSs both inside and outside class to avoid boundary and privacy issues as well as deviation from the initial lesson objectives.

11.
Physiother Theory Pract ; : 1-7, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36734244

RESUMO

BACKGROUND: Previous studies reported inconsistent outcomes on elastic taping for three potential reasons: 1) poor control of placebo effect; 2) no consensus regarding the optimal tape tension; and 3) lack of investigation on muscle endurance, as the proposed tape recoiling force may not promote peak force generation but exert a consistently low force and improve submaximal contraction. PURPOSE: This study compared the effects of elastic tape and its tension on muscle activity and endurance in people with extremely positive and negative personal belief on elastic tape. METHODS: Using a validated instrument, we identified 20 participants with extremely positive personal belief on elastic tape (+ belief), and 20 with extremely negative personal belief (- belief). They performed wrist isometric endurance tests under three taping conditions (i.e. no tape, 50%, and 100% tension). We measured isometric wrist extensor muscle endurance, electromyography muscle activity, and self-perceived performance for each condition. RESULTS: The differences between the two groups in isometric muscle endurance (p = .85) and muscle activity (p = .53) were not statistically significant, regardless of tape conditions. However, participants with + belief reported better perceived performance than those with - belief (p < .001, partial eta squared = 0.70). Specifically, 100% tape tension yielded stronger self-perceived performance than 50% tension (Cohen's d = 0.91) and no tape (Cohen's d = 1.86). On the other hand, participants with - belief perceived similar performance across tape tensions (p = .55). CONCLUSION: Elastic tape does not modulate muscle activity and enhance muscle endurance. People with a strong positive personal belief on elastic tape may perceive a better performance with a greater tape tension.

12.
Hand (N Y) ; : 15589447221150506, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36692096

RESUMO

BACKGROUND: Radial height is a radiographic parameter used to guide the treatment of distal radius fractures. However, it is often used synonymously with other terms, and there are substantial discrepancies in its measurement/definition. These discrepancies can alter the measurement of radial height and affect treatment decisions. The purpose of this review is to identify the different definitions of radial height in the literature relevant to distal radius fractures. METHODS: A literature review was conducted in the PubMed/MEDLINE database from inception to 2022. Full-length, English-language studies that pertained to distal radius fractures and reported radial height as a recorded measurement were included. The method of radial height measurement (definition) was extracted from included studies. Level of evidence was determined by the Oxford Centre for Evidence-based Medicine Levels of Evidence tool. RESULTS: A total of 385 studies were identified. Of these, 183 (47.5%) did not provide a definition for radial height. Of the studies that defined radial height, 50.9% (103/202) measured radial height from the radial styloid to the distal ulna, 10.9% (22/202) measured from the radial styloid to the distal radius, and 29.2% (59/202) were "other" definitions. CONCLUSIONS: There is substantial discrepancy in the way that radial height is measured and reported. We advocate for a standardized measurement of radial height (synonymous with radial length) from the radial styloid to the distal ulnar articular surface. Radial shortening is a different measurement and requires comparison with a reference value.

13.
Clin Epigenetics ; 15(1): 5, 2023 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611168

RESUMO

BACKGROUND: Combination chemotherapy has contributed to increased survival from Hodgkin disease (HD) and testicular cancer (TC). However, questions concerning the quality of spermatozoa after treatment have arisen. While studies have shown evidence of DNA damage and aneuploidy in spermatozoa years following anticancer treatment, the sperm epigenome has received little attention. Our objectives here were to determine the impact of HD and TC, as well as their treatments, on sperm DNA methylation. Semen samples were collected from community controls (CC) and from men undergoing treatment for HD or TC, both before initiation of chemotherapy and at multiple times post-treatment. Sperm DNA methylation was assessed using genome-wide and locus-specific approaches. RESULTS: Imprinted gene methylation was not affected in the sperm of HD or TC men, before or after treatment. Prior to treatment, using Illumina HumanMethylation450 BeadChip (450 K) arrays, a subset of 500 probes was able to distinguish sperm samples from TC, HD and CC subjects; differences between groups persisted post-treatment. Comparing altered sperm methylation between HD or TC patients versus CC men, twice as many sites were affected in TC versus HD men; for both groups, the most affected CpGs were hypomethylated. For TC patients, the promoter region of GDF2 contained the largest region of differential methylation. To assess alterations in DNA methylation over time/post-chemotherapy, serial samples from individual patients were compared. With restriction landmark genome scanning and 450 K array analyses, some patients who underwent chemotherapy showed increased alterations in DNA methylation, up to 2 to 3 years post-treatment, when compared to the CC cohort. Similarly, a higher-resolution human sperm-specific assay that includes assessment of environmentally sensitive regions, or "dynamic sites," also demonstrated persistently altered sperm DNA methylation in cancer patients post-treatment and suggested preferential susceptibility of "dynamic" CpG sites. CONCLUSIONS: Distinct sperm DNA methylation signatures were present pre-treatment in men with HD and TC and may help explain increases in birth defects reported in recent clinical studies. Epigenetic defects in spermatozoa of some cancer survivors were evident even up to 2 years post-treatment. Abnormalities in the sperm epigenome both pre- and post-chemotherapy may contribute to detrimental effects on future reproductive health.


Assuntos
Doença de Hodgkin , Neoplasias Testiculares , Humanos , Masculino , Epigenoma , Sêmen , Metilação de DNA , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/genética , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/genética , Doença de Hodgkin/metabolismo , Espermatozoides/metabolismo
14.
Tech Hand Up Extrem Surg ; 27(2): 125-130, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36534764

RESUMO

Dupuytren disease and its associated digit contracture often negatively impact the quality of life for patients. Severe cases of Dupuytren contracture and symptom recurrence are both difficult for hand surgeons to treat. Improved treatment options are therefore needed. One method is continuous passive elongation (CPE). In CPE, a device is affixed to the digit, which applies a continuous extending force to pull the affected finger out of flexion. Multiple external fixators used to induce CPE have been reported. However, a low-profile, hand-specific external fixator, the DigiFix, provides benefits over previously reported devices. We present the technique of CPE using DigiFix as a beneficial and versatile adjunct treatment for severe and recurrent cases of Dupuytren contracture.


Assuntos
Contratura de Dupuytren , Humanos , Contratura de Dupuytren/cirurgia , Qualidade de Vida , Recidiva Local de Neoplasia , Dedos , Fixadores Externos , Resultado do Tratamento
15.
Aust Crit Care ; 36(1): 92-98, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36244918

RESUMO

BACKGROUND: Caregiver workload in the ICU setting is difficult to numerically quantify. Ambient Intelligence utilises computer vision-guided neural networks to continuously monitor multiple datapoints in video feeds, has become increasingly efficient at automatically tracking various aspects of human movement. OBJECTIVES: To assess the feasibility of using Ambient Intelligence to track and quantify allpatient and caregiver activity within a bedspace over the course of an ICU admission and also to establish patient specific factors, and environmental factors such as time ofday, that might contribute to an increased workload in ICU workers. METHODS: 5000 images were manually annotated and then used to train You Only LookOnce (YOLOv4), an open-source computer vision algorithm. Comparison of patientmotion and caregiver activity was then performed between these patients. RESULTS: The algorithm was deployed on 14 patients comprising 1762800 framesof new, untrained data. There was a strong correlation between the number ofcaregivers in the room and the standardized movement of the patient (p < 0.0001) withmore caregivers associated with more movement. There was a significant difference incaregiver activity throughout the day (p < 0.05), HDU vs. ICU status (p < 0.05), delirious vs. non delirious patients (p < 0.05), and intubated vs. not intubated patients(p < 0.05). Caregiver activity was lowest between 0400 and 0800 (average .71 ± .026caregivers per hour) with statistically significant differences in activity compared to 0800-2400 (p < 0.05). Caregiver activity was highest between 1200 and 1600 (1.02 ± .031 caregivers per hour) with a statistically significant difference in activity comparedto activity from 1600 to 0800 (p < 0.05). The three most dominant predictors of workeractivity were patient motion (Standardized Dominance 78.6%), Mechanical Ventilation(Standardized Dominance 7.9%) and Delirium (Standardized Dominance 6.2%). CONCLUSION: Ambient Intelligence could potentially be used to derive a single standardized metricthat could be applied to patients to illustrate their overall workload. This could be usedto predict workflow demands for better staff deployment, monitoring of caregiver workload, and potentially as a tool to predict burnout.


Assuntos
Inteligência Ambiental , Cuidados Críticos , Humanos , Unidades de Terapia Intensiva , Hospitalização , Carga de Trabalho
16.
Educ Inf Technol (Dordr) ; 28(1): 193-216, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35789767

RESUMO

Coding games are widely used to teach computational thinking (CT). Studies have broadly investigated the role of coding games in supporting CT learning in formal classroom contexts, but there has been limited exploration of their use in informal home-based settings. This study investigated the factors that motivated students to use a coding game called Coding Galaxy in a home-based setting. It explored the connections between the students' perceptions of and usage of the tool. An 11-day intervention was conducted at a primary school in Hong Kong with 104 participants. The students' perceptions of the game were collected via questionnaires and information on their use of the tool was extracted from log files. Results indicated that coding motivation and feeling of enjoyment were predictors of the actual use of the game, with coding motivation the dominant factor. Focus group interviews were also conducted to further explore the students' motivation to play the game. Through comparisons of active and inactive users, the qualitative findings supported the quantitative results, indicating that students who were more intrinsically motivated tended to be more active in using the game. The implications of the study for researchers and practitioners in CT education are discussed.

17.
Sports Biomech ; 22(3): 459-472, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35232315

RESUMO

This study investigated treadmill familiarisation time in different shoe conditions by comparing lower limb consecutive kinematics waveforms using a trend symmetry method to calculate trend symmetry index, range amplitude ratio and range offset. Eighteen young adults (26.6 ± 3.3 years, 7 females) completed three 10-minute running trials at their preferred running speed (2.30 ± 0.17 m/s) on a treadmill with three shoe conditions (i.e., usual, minimalist and maximalist shoes) in a random order. Sagittal lower limb kinematic data were recorded using inertial measurement units. The results showed that sagittal-plane kinematic waveforms in the hip, knee and ankle remained consistent (trend symmetry > 0.95) without extreme excursions (range amplitude ratio ≈ 1) over 10 minutes within each testing shoe condition. Significant time × shoe interaction effect was observed in range offset (i.e., absolute differences in the average degree of kinematic waveforms between consecutive minutes) at ankle (p = 0.029, ŋp2 = 0.096) and knee (p = 0.002, ŋp2 = 0.126). Post-hoc analysis suggested that running with novel shoes required a shorter time to achieve stable lower limb kinematics (2 to 3 minutes) compared with usual shoes (7 minutes). In conclusion, young healthy adults need up to 3 and 7 minutes to familiarise to the treadmill when running at their preferred speed with their novel and usual running shoes.


Assuntos
, Corrida , Feminino , Adulto Jovem , Humanos , Sapatos , Fenômenos Biomecânicos , Extremidade Inferior , Marcha
18.
Hand (N Y) ; 18(1): NP1-NP4, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35354344

RESUMO

The most common cause for catching or snapping in the finger is stenosing tenosynovitis, that is, trigger finger. Although less common, snapping can also occur as a result of extensor mechanism injury. Among these injuries, sagittal band rupture is most common and leads to snapping at the metacarpophalangeal joint. Snapping at the proximal interphalangeal (PIP) joint is rare with only 4 reported cases; reported mechanisms of PIP joint snapping include retinacular ligament injury or tendon impingement. We present a unique case of painful finger snapping at the PIP joint as a result of longitudinal tear of the central slip, leading to sudden subluxation of one-half of the central slip and conjoint lateral band with flexion of the PIP joint.


Assuntos
Traumatismos dos Dedos , Luxações Articulares , Lacerações , Humanos , Dedos/cirurgia , Traumatismos dos Dedos/complicações , Traumatismos dos Dedos/cirurgia , Tendões
19.
Org Biomol Chem ; 21(1): 153-162, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36472095

RESUMO

The disordered tubulin C-terminal tail (CTT), which possesses a higher degree of heterogeneity, is the target for the interaction of many proteins and cellular components. Compared to the seven well-described binding sites of microtubule-targeting agents (MTAs) that localize on the globular tubulin core, tubulin CTT is far less explored. Therefore, tubulin CTT can be regarded as a novel site for the development of MTAs with distinct biochemical and cell biological properties. Here, we designed and synthesized linear and cyclic peptides containing multiple arginines (RRR), which are complementary to multiple acidic residues in tubulin CTT. Some of them showed moderate induction and promotion of tubulin polymerization. The most potent macrocyclic compound 1f was found to bind to tubulin CTT and thus exert its bioactivity. Such RRR containing compounds represent a starting point for the discovery of tubulin CTT-targeting agents with therapeutic potential.


Assuntos
Antineoplásicos , Tubulina (Proteína) , Tubulina (Proteína)/metabolismo , Microtúbulos/metabolismo , Antineoplásicos/farmacologia , Sítios de Ligação , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/metabolismo
20.
Cancers (Basel) ; 14(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36497445

RESUMO

Eribulin is a microtubule destabilizer used in the treatment of triple-negative breast cancer (TNBC). Eribulin and other microtubule targeted drugs, such as the taxanes, have shared antimitotic effects, but differ in their mechanism of microtubule disruption, leading to diverse effects on cellular signaling and trafficking. Herein, we demonstrate that eribulin is unique from paclitaxel in its ability to enhance expression of the immunogenic cytokine interferon beta (IFNß) in combination with STING agonists in both immune cells and TNBC models, including profound synergism with ADU-S100 and E7766, which are currently undergoing clinical trials. The mechanism by which eribulin enhances STING signaling is downstream of microtubule disruption and independent of the eribulin-dependent release of mitochondrial DNA. Eribulin did not override the requirement of ER exit for STING activation and did not inhibit subsequent STING degradation; however, eribulin significantly enhanced IRF3 phosphorylation and IFNß production downstream of the RNA sensing pathway that converges on this transcription factor. Additionally, we found that eribulin enhanced the population of activated CD4+ T-cells in vivo when combined with either a STING agonist or tumor, demonstrating the ability to function as an immune adjuvant. We further interrogated the combination of eribulin with ADU-S100 in the MMTV-PyVT spontaneous murine mammary tumor model where we observed significant antitumor efficacy with combination treatment. Together, our findings demonstrate that microtubule targeted chemotherapeutics have distinct immunological effects and that eribulin's ability to enhance innate immune sensing pathways supports its use in combination with immunotherapies, such as STING agonists, for the more effective treatment of TNBC and other malignancies.

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