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1.
Clin Neurol Neurosurg ; 246: 108563, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39299006

RESUMO

OBJECTIVE: The prevalence of chronic pain in Parkinson's disease (PD) in neurology practices ranges from 24 % to 83 %. To determine whether this prevalence is accurate across patients with PD, we leveraged data from electronic medical records in 80 inpatient and outpatient general practice settings. METHODS: We explored the prevalence of chronic pain in patients with PD relative to age and sex-matched controls in a large international database with electronic medical records from over 250 million patients (TriNetX Cambridge, MA, USA). We described demographics, co-morbid conditions and medication differences between patients with PD and without PD who have chronic pain. RESULTS: Extracted data included 4510 patients with PD and 4,214,982 age-matched control patients without Parkinson's Disease. A chronic pain diagnosis was identified in 19.3 % of males and 22.8 % of females with PD. This differed significantly from age-matched patients without PD who had a significantly lower prevalence of chronic pain 3.78 % and 4.76 %. Significantly more PD patients (both male and females) had received tramadol, oxycodone, and neuropathic agents (p<0.001) than patients without PD. Females with PD more often received anti-depressants than males with PD (p<0.05), corresponding with a significantly higher prevalence of depression. CONCLUSION: Chronic pain in patients with PD is five times as common as in age-matched controls in general practice settings. Patients with PD have a greater prevalence of comorbid conditions that affect development of chronic pain. Whether the pain or the PD is causative to those conditions remains to be elucidated.

2.
J Mol Cell Cardiol ; 196: 105-114, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276853

RESUMO

Improving energy provision in the failing heart by augmenting the creatine kinase (CK) system is a desirable therapeutic target. However, over-expression of the creatine transporter (CrT-OE) has shown that very high creatine levels result in cardiac hypertrophy and dysfunction. We hypothesise this is due to insufficient endogenous CK activity to maintain thermodynamically favourable metabolite ratios. If correct, then double transgenic mice (dTg) overexpressing both CrT and the muscle isoform of CK (CKM-OE) would rescue the adverse phenotype. In Study 1, overexpressing lines were crossed and cardiac function assessed by invasive haemodynamics and echocardiography. This demonstrated that CKM-OE was safe, but too few hearts had creatine in the toxic range. In Study 2, a novel CrT-OE line was generated with higher, homogeneous, creatine levels and phenotyped as before. Myocardial creatine was 4-fold higher in CrT-OE and dTg hearts compared to wildtype and was associated with hypertrophy and contractile dysfunction. The inability of dTg hearts to rescue this phenotype was attributed to downregulation of CK activity, as occurs in the failing heart. Nevertheless, combining both studies in a linear regression analysis suggests a modest positive effect of CKM over a range of creatine concentrations. In conclusion, we confirm that moderate elevation of creatine is well tolerated, but very high levels are detrimental. Correlation analysis lends support to the theory that this may be a consequence of limited CK activity. Future studies should focus on preventing CKM downregulation to unlock the potential synergy of augmenting both creatine and CK in the heart.

3.
Drugs ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240532
4.
Immunol Rev ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248154

RESUMO

Following success in cancer immunotherapy, immune checkpoint blockade is emerging as an exciting potential treatment for some infectious diseases, specifically two chronic viral infections, HIV and hepatitis B. Here, we will discuss the function of immune checkpoints, their role in infectious disease pathology, and the ability of immune checkpoint blockade to reinvigorate the immune response. We focus on blockade of programmed cell death 1 (PD-1) to induce durable immune-mediated control of HIV, given that anti-PD-1 can restore function to exhausted HIV-specific T cells and also reverse HIV latency, a long-lived form of viral infection. We highlight several key studies and future directions of research in relation to anti-PD-1 and HIV persistence from our group, including the impact of immune checkpoint blockade on the establishment (AIDS, 2018, 32, 1491), maintenance (PLoS Pathog, 2016, 12, e1005761; J Infect Dis, 2017, 215, 911; Cell Rep Med, 2022, 3, 100766) and reversal of HIV latency (Nat Commun, 2019, 10, 814; J Immunol, 2020, 204, 1242), enhancement of HIV-specific T cell function (J Immunol, 2022, 208, 54; iScience, 2023, 26, 108165), and investigating the effects of anti-PD-1 and anti-CTLA-4 in vivo in people with HIV on ART with cancer (Sci Transl Med, 2022, 14, eabl3836; AIDS, 2021, 35, 1631; Clin Infect Dis, 2021, 73, e1973). Our future work will focus on the impact of anti-PD-1 in vivo in people with HIV on ART without cancer and potential combinations of anti-PD-1 with other interventions, including therapeutic vaccines or antibodies and less toxic immune checkpoint blockers.

5.
Ann Neurol ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39263992

RESUMO

OBJECTIVES: Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions. METHODS: We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States. Clinical manifestations and patient demographics were collected retrospectively from clinical records in an unblinded approach using a standardized form. Post-mortem analysis was done on 4 brains of patients with genetically confirmed SCA27B. RESULTS: In our cohort of 102 patients with SCA27B, we found that SCA27B was a late-onset (57 ± 12.5 years) slowly progressive ataxia with an episodic component in 51% of patients. Balance and gait impairment were almost always present at disease onset. The principal finding on post-mortem examination of 4 brain specimens was loss of Purkinje neurons that was most severe in the vermis most particularly in the anterior vermis. Similar to European populations, a high percent of patients 21/28 (75%) reported a positive treatment response with 4-aminopyridine. INTERPRETATION: Our study further estimates prevalence and further expands the clinical, imaging and pathological features of SCA27B, while looking at treatment response, disease progression, and survival in patients with this disease. Testing for SCA27B should be considered in all undiagnosed ataxia patients, especially those with episodic onset. ANN NEUROL 2024.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39265080

RESUMO

Local renin-angiotensin signaling is present within various organ systems of the body. Angiotensin II signaling acts as a crucial mechanism of the renin-angiotensin signaling system. In this manuscript, we review current literature regarding local angiotensin II signaling in the urinary bladder. Our interest in this pathway is due to its potential role in interstitial cystitis/bladder pain syndrome and other bladder diseases, which are chronic in nature and negatively affect patients' quality of life. Current treatments for bladder diseases are generally ineffective due to our lack of understanding of their pathophysiology. We evaluate literature investigating angiotensin II signaling in the bladder across several perspectives, including local expression and production, functional properties, tissue morphology, and clinical implications. Further, we identify gaps in knowledge and suggest areas where we can improve our understanding of angiotensin II signaling in the bladder.

7.
Brain Commun ; 6(5): fcae298, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39262826

RESUMO

Delirium is a common and acute neurocognitive disorder in older adults associated with increased risk of dementia and death. Understanding the interaction between brain vulnerability and acute stressors is key to delirium pathophysiology, but the neurophysiology of delirium vulnerability is not well defined. This study aimed to identify pre-operative resting-state EEG and event-related potential markers of incident delirium and its subtypes in older adults undergoing elective cardiac procedures. This prospective observational study included 58 older participants (mean age = 75.6 years, SD = 7.1; 46 male/12 female); COVID-19 restrictions limited recruitment. Baseline assessments were conducted in the weeks before elective cardiac procedures and included a 4-min resting-state EEG recording (2-min eyes open and 2-min eyes closed), a 5-min frequency auditory oddball paradigm recording, and cognitive and depression examinations. Periodic peak power, peak frequency and bandwidth measures, and aperiodic offsets and exponents were derived from resting-state EEG data. Event-related potentials were measured as mean component amplitudes (first positive component, first negative component, early third positive component, and mismatch negativity) following standard and deviant auditory stimuli. Incident delirium occurred in 21 participants: 10 hypoactive, 6 mixed, and 5 hyperactive. Incident hyperactive delirium was associated with higher pre-operative eyes open (P = 0.045, d = 1.0) and closed (P = 0.036, d = 1.0) aperiodic offsets. Incident mixed delirium was associated with significantly larger pre-operative first positive component amplitudes to deviants (P = 0.037, d = 1.0) and larger third positive component amplitudes to standards (P = 0.025, d = 1.0) and deviants (P = 0.041, d = 0.9). Other statistically non-significant but moderate-to-large effects were observed in relation to all subtypes. We report evidence of neurophysiological markers of delirium risk weeks prior to elective cardiac procedures in older adults. Despite being underpowered due to COVID-19-related recruitment impacts, these findings indicate pre-operative dysfunction in neural excitation/inhibition balance associated with different delirium subtypes and warrant further investigation on a larger scale.

8.
bioRxiv ; 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39131334

RESUMO

T cells and structural cells coordinate appropriate inflammatory responses and restoration of barrier integrity following insult. Dysfunctional T cell activity precipitates tissue pathology that occurs alongside disease-associated alterations of structural cell subsets, but the mechanisms by which T cells promote these changes remain unclear. We show that subsets of circulating and skin-resident CD4+ T cells promote distinct transcriptional outcomes in human keratinocytes and dermal fibroblasts that correspond with divergent T cell cytokine production. Using these transcriptional signatures, we identify T cell-dependent outcomes associated with inflammatory skin disease, including a set of Th17 cell-induced genes in keratinocytes that are enriched in the skin during psoriasis and normalized by anti-IL-17 therapy, and a skin-resident T cell-induced gene module enriched in scleroderma-associated fibroblasts. Interrogating clinical data using T cell-derived structural cell gene networks enables investigation of the immune-dependent contribution to inflammatory disease and the heterogeneous patient response to biologic therapy.

9.
Orthopedics ; 47(5): e217-e224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39163602

RESUMO

BACKGROUND: The recent addition of biceps tendon augmentation to partial arthroscopic rotator cuff repair (ARCR) for the treatment of large-to-massive rotator cuff tears is proposed to improve clinical outcomes and reduce re-tears. MATERIALS AND METHODS: The purpose of this systematic review and meta-analysis (5 studies) was to compare outcomes between partial ARCR with (142 patients) and without (149 patients) biceps augmentation. RESULTS: Partial ARCR with and without biceps augmentation were comparable in pain, function, and range of motion. However, biceps augmentation vs no augmentation at all during ARCR may lower re-tear rates for irreparable large-to-massive rotator cuff tears (42.9% vs 72.5%, P=.007). CONCLUSION: More research is needed to investigate this technique and guide surgical decision-making. [Orthopedics. 2024;47(5):e217-e224.].


Assuntos
Artroscopia , Lesões do Manguito Rotador , Humanos , Lesões do Manguito Rotador/cirurgia , Artroscopia/métodos , Resultado do Tratamento , Manguito Rotador/cirurgia
10.
bioRxiv ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39211224

RESUMO

Background: Increases in GPNMB are detectable in FTD- GRN cerebrospinal fluid (CSF) and post-mortem brain, and brains of aged Grn -deficient mice. Although no upregulation of GPNMB is observed in the brains of young Grn -deficient mice, peripheral immune cells of these mice do exhibit this increase in GPNMB. Importantly, the functional significance of GPNMB upregulation in progranulin-deficient states is currently unknown. Given that GPNMB has been discussed as a potential therapeutic target in GRN -mediated neurodegeneration, it is vital for the field to determine what the normal function of GPNMB is in the immune system, and whether targeting GPNMB will elicit beneficial or deleterious effects. Methods: The effects of GPNMB knock-down via antisense oligonucleotide (ASO) were assessed in peripheral blood mononuclear cells (PBMCs) from 25 neurologically healthy controls (NHCs) and age- and sex-matched FTD- GRN patients, as well as peritoneal macrophages (pMacs) from progranulin-deficient ( Grn -/- ) and B6 mice. Lysosomal function, antigen presentation and MHC-II processing and recycling were assessed, as well as cytokine release and transcription. Results: We demonstrate here that ASO-mediated knockdown of GPNMB increases lysosomal burden and cytokine secretion in FTD-GRN carrier and neurologically healthy controls (NHCs) monocytes. ASO-mediated knockdown of GPNMB in Grn -deficient macrophages decreased lysosomal pan-cathepsin activity and protein degradation. In addition, ASO-mediated knockdown of GPNMB increased MHC-II surface expression, which was driven by decreased MHC-II uptake and recycling, in macrophages from Grn -deficient females. Finally, ASO-mediated knockdown of GPNMB dysregulated IFNγ-stimulated cytokine transcription and secretion by mouse macrophages due to the absence of regulatory actions of the GPNMB extracellular fragment (ECF). Conclusions: Our data herein reveals that GPNMB has a regulatory effect on multiple immune effector functions, including capping inflammation and immune responses in myeloid cells via secretion of its ECF. Therefore, in progranulin-deficient states, the drastic upregulation in GPNMB transcript and protein may represent a compensatory mechanism to preserve lysosomal function in myeloid cells. These novel findings indicate that targeted depletion in FTD- GRN would not be a rational therapeutic strategy because it is likely to dysregulate important immune cell effector functions.

11.
Drugs ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39110316

RESUMO

Elafibranor (IQIRVO®) is a first-in-class peroxisome proliferator-activated receptor (PPAR) agonist being developed by Ipsen, under license from Genfit, for the treatment of primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). On 10 June 2024, elafibranor received accelerated approval based on reduction of alkaline phosphatase (ALP) in the USA for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. Elafibranor has also received a positive opinion in the EU. This article summarizes the milestones in the development of elafibranor leading to this first approval for PBC.

12.
Clin Drug Investig ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167354
13.
Clin Spine Surg ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101583

RESUMO

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate for areas of consensus and divergence of opinion within the spine community regarding the management of cervical spondylotic conditions and acute traumatic central cord syndrome (ATCCS) and the influence of the patient's age, disease severity, and myelomalacia. SUMMARY OF BACKGROUND DATA: There is ongoing disagreement regarding the indications for, and urgency of, operative intervention in patients with mild degenerative myelopathy, moderate to severe radiculopathy, isolated axial symptomatology with evidence of spinal cord compression, and ATCCS without myelomalacia. METHODS: A survey request was sent to 330 attendees of the Cervical Spine Research Society (CSRS) 2021 Annual Meeting to assess practice patterns regarding the treatment of cervical stenosis, myelopathy, radiculopathy, and ATCCS in 16 unique clinical vignettes with associated MRIs. Operative versus nonoperative treatment consensus was defined by a management option selected by >80% of survey participants. RESULTS: Overall, 116 meeting attendees completed the survey. Consensus supported nonoperative management for elderly patients with axial neck pain and adults with axial neck pain without myelomalacia. Operative management was indicated for adult patients with mild myelopathy and myelomalacia, adult patients with severe radiculopathy, elderly patients with severe radiculopathy and myelomalacia, and elderly ATCCS patients with pre-existing myelopathic symptoms. Treatment discrepancy in favor of nonoperative management was found for adult patients with isolated axial symptomatology and myelomalacia. Treatment discrepancy favored operative management for elderly patients with mild myelopathy, adult patients with mild myelopathy without myelomalacia, elderly patients with severe radiculopathy without myelomalacia, and elderly ATCCS patients without preceding symptoms. CONCLUSIONS: Although there is uncertainty regarding the treatment of mild myelopathy, operative intervention was favored for nonelderly patients with evidence of myelomalacia or radiculopathy and for elderly patients with ATCCS, especially if pre-injury myelopathic symptoms were present. LEVEL OF EVIDENCE: Level V.

15.
J Am Acad Orthop Surg ; 32(18): e940-e950, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008910

RESUMO

INTRODUCTION: The factors most important in the spine fellowship match may not ultimately correlate with quality of performance during fellowship. This study examined the spine fellow applicant metrics correlated with high application rank compared with the metrics associated with the strongest clinical performance during fellowship. METHODS: Spine fellow applications at three academic institutions were retrieved from the San Francisco Match database (first available to 2021) and deidentified for application review. Application metrics pertaining to research, academics, education, extracurriculars, leadership, examinations, career interests, and letter of recommendations were extracted. Attending spine surgeons involved in spine fellow selection at their institutions were sent a survey to rank (1) fellow applicants based on their perceived candidacy and (2) the strength of performance of their previous fellows. Pearson correlation assessed the associations of application metrics with theoretical fellow rank and actual performance. RESULTS: A total of 37 spine fellow applications were included (Institution A: 15, Institution B: 12, Institution C: 10), rated by 14 spine surgeons (Institution A: 6, Institution B: 4, Institution C: 4). Theoretical fellow rank demonstrated a moderate positive association with overall research, residency program rank, recommendation writer H-index, US Medical Licensing Examination (USMLE) scores, and journal reviewer positions. Actual fellow performance demonstrated a moderate positive association with residency program rank, recommendation writer H-index, USMLE scores, and journal reviewer positions. Linear regressions identified journal reviewer positions (ß = 1.73, P = 0.002), Step 1 (ß = 0.09, P = 0.010) and Step 3 (ß = 0.10, P = 0.002) scores, recommendation writer H-index (ß = 0.06, P = 0.029, and ß = 0.07, P = 0.006), and overall research (ß = 0.01, P = 0.005) as predictors of theoretical rank. Recommendation writer H-index (ß = 0.21, P = 0.030) and Alpha Omega Alpha achievement (ß = 6.88, P = 0.021) predicted actual performance. CONCLUSION: Residency program reputation, USMLE scores, and a recommendation from an established spine surgeon were important in application review and performance during fellowship. Research productivity, although important during application review, was not predictive of fellow performance. LEVEL OF EVIDENCE: III. STUDY DESIGN: Cohort Study.


Assuntos
Competência Clínica , Bolsas de Estudo , Internato e Residência , Coluna Vertebral , Humanos , Coluna Vertebral/cirurgia , Ortopedia/educação , Inquéritos e Questionários , Educação de Pós-Graduação em Medicina
16.
mBio ; 15(8): e0078224, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-38953639

RESUMO

Copious amounts of methane, a major constituent of greenhouse gases currently driving climate change, are emitted by livestock, and efficient methods that curb such emissions are urgently needed to reduce global warming. When fed to cows, the red seaweed Asparagopsis taxiformis (AT) can reduce enteric methane emissions by up to 80%, but the achieved results can vary widely. Livestock produce methane as a byproduct of methanogenesis, which occurs during the breakdown of feed by microbes in the rumen. The ruminant microbiome is a diverse ecosystem comprising bacteria, protozoa, fungi, and archaea, and methanogenic archaea work synergistically with bacteria to produce methane. Here, we find that an effective reduction in methane emission by high-dose AT (0.5% dry matter intake) was associated with a reduction in methanol-utilizing Methanosphaera within the rumen, suggesting that they may play a greater role in methane formation than previously thought. However, a later spike in Methanosphaera suggested an acquired resistance, possibly via the reductive dehalogenation of bromoform. While we found that AT inhibition of methanogenesis indirectly impacted ruminal bacteria and fermentation pathways due to an increase in spared H2, we also found that an increase in butyrate synthesis was due to a direct effect of AT on butyrate-producing bacteria such as Butyrivibrio, Moryella, and Eubacterium. Together, our findings provide several novel insights into the impact of AT on both methane emissions and the microbiome, thereby elucidating additional pathways that may need to be targeted to maintain its inhibitory effects while preserving microbiome health and animal productivity. IMPORTANCE: Livestock emits copious quantities of methane, a major constituent of the greenhouse gases currently driving climate change. Methanogens within the bovine rumen produce methane during the breakdown of feed. While the red seaweed Asparagopsis taxiformis (AT) can significantly reduce methane emissions when fed to cows, its effects appear short-lived. This study revealed that the effective reduction of methane emissions by AT was accompanied by the near-total elimination of methane-generating Methanosphaera. However, Methanosphaera populations subsequently rebounded due to their ability to inactivate bromoform, a major inhibitor of methane formation found in AT. This study presents novel findings on the contribution of Methanosphaera to ruminal methanogenesis, the mode of action of AT, and the possibility for complementing different strategies to effectively curb methane emissions.


Assuntos
Metano , Rúmen , Animais , Metano/metabolismo , Bovinos , Rúmen/microbiologia , Bactérias/classificação , Bactérias/metabolismo , Bactérias/genética , Microbioma Gastrointestinal , Microbiota , Archaea/metabolismo , Archaea/classificação , Archaea/genética , Alga Marinha/metabolismo , Rodófitas/metabolismo , Ração Animal/análise , Fermentação
17.
Clin Drug Investig ; 44(7): 549-552, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38963659

RESUMO

AVT04 (Uzpruvo®) is a biosimilar of the reference anti-interleukin (IL)-12 and IL-23 monoclonal antibody ustekinumab. It is approved in the EU for plaque psoriasis, paediatric plaque psoriasis, psoriatic arthritis and Crohn's disease as per the reference product. AVT04 has similar physicochemical characteristics to those of reference ustekinumab, and the pharmacokinetic similarity of the agents has been shown in healthy volunteers and patients with moderate to severe chronic plaque psoriasis. AVT04 demonstrated clinical efficacy similar to that of reference ustekinumab in patients with moderate to severe chronic plaque psoriasis, and was generally well tolerated in this population. The tolerability, safety and immunogenicity profiles of AVT04 were similar to those of reference ustekinumab, and switching from reference ustekinumab to AVT04 had no impact on efficacy, safety or immunogenicity. The role of reference ustekinumab in the management of inflammatory diseases is well established and AVT04 provides an effective biosimilar alternative for patients requiring ustekinumab therapy.


Assuntos
Medicamentos Biossimilares , Psoríase , Ustekinumab , Humanos , Ustekinumab/uso terapêutico , Ustekinumab/farmacocinética , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/farmacocinética , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/farmacologia , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/farmacocinética , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacologia , Doença de Crohn/tratamento farmacológico
18.
J Equine Vet Sci ; 139: 105146, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38960010

RESUMO

Intercollegiate Horse Show Association (IHSA) competitions evaluate riders on equitation and skills when riding randomly drawn horses. This study considered demographic and competition-related variables of horses involved in IHSA competitions, and their correlation to performance through points accumulated. Demographics were recorded for fifty-nine horses in two-day Hunter Seat and Western IHSA shows along with use of artificial riding aids, day of competition, number of rides, and points, to evaluate performance. Data were analyzed using a mixed effect model and correlation coefficients with significance set at P < 0.05 (SAS 9.4). Hunter Seat horses averaged more rides per day than Western (P < 0.0001), but points per ride were not different between disciplines (P = 0.57) or days of shows (P = 0.47). Use of artificial aids did not impact points per ride a horse accumulated (P = 0.63 Hunter Seat, P = 0.41 Western). Age, (r = -0.10, P = 0.60; r = 0.02, P = 0.90), BCS (r = 0.15, P = 0.42; r = 0.17, P = 0.34), height (r = 0.20, P = 0.28; r = 0.15, P = 0.39), and weight (r = 0.23, P = 0.23; r = 0.20, P = 0.25) were weakly correlated with points earned for Hunter Seat and Western horses, respectively. Random draw in IHSA is suggested to be effective for equitation competitions, allowing a fair opportunity for riders, regardless of the horse-related factors evaluated in this study.


Assuntos
Esportes , Cavalos/fisiologia , Animais , Masculino , Feminino
19.
BioDrugs ; 38(5): 717-724, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39031321

RESUMO

Insulin icodec (AWIQLI®) is an ultra-long-acting basal insulin analogue that is being developed by Novo Nordisk for the treatment of diabetes mellitus. Administered once weekly as a subcutaneous injection, insulin icodec is designed to improve treatment adherence and glycaemic control relative to once-daily insulin analogues. On 7 March 2024, insulin icodec was approved in Switzerland for the treatment of diabetes mellitus in adults. Insulin icodec was approved in Canada on 12 March 2024 for the once-weekly treatment of adults with diabetes mellitus to improve glycaemic control and received EU approval in May 2024 for the treatment of diabetes mellitus in adults. This article summarizes the milestones in the development of insulin icodec leading to this first approval for diabetes mellitus.


Assuntos
Aprovação de Drogas , Hipoglicemiantes , Humanos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/administração & dosagem , Injeções Subcutâneas , Canadá , Diabetes Mellitus/tratamento farmacológico , Insulina de Ação Prolongada/uso terapêutico , Insulina/uso terapêutico , Insulina/análogos & derivados , Insulina/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico
20.
Eur Spine J ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39014077

RESUMO

PURPOSE: To determine of the impact of ALIF with minimally invasive unilateral pedicle screw fixation (UPSF) versus bilateral pedicle screw fixation (BPSF) on perioperative outcomes, radiographic outcomes, and the rates of fusion, subsidence, and adjacent segment stenosis. METHODS: All adult patients who underwent one-level ALIF with UPSF or BPSF at an academic institution between 2015 and 2022 were retrospectively identified. Postoperative outcomes including length of hospital stay (LOS), wound complications, readmissions, and revisions were determined. The rates of fusion, screw loosening, adjacent segment stenosis, and subsidence were assessed on one-year postoperative CT. Lumbar alignment including lumbar lordosis, L4-S1 lordosis, regional lordosis, pelvic tilt, pelvic incidence, and sacral slope were assessed on standing x-rays at preoperative, immediate postoperative, and final postoperative follow-up. Univariate and multivariate analysis compared outcomes across posterior fixation groups. RESULTS: A total of 60 patients were included (27 UPSF, 33 BPSF). Patients with UPSF were significantly younger (p = 0.011). Operative time was significantly greater in the BPSF group in univariate (p < 0.001) and multivariate analysis (ß=104.1, p < 0.001). Intraoperative blood loss, LOS, lordosis, pelvic parameters, fusion rate, subsidence, screw loosening, adjacent segment stenosis, and revision rate did not differ significantly between fixation groups. Though sacral slope (p = 0.037) was significantly greater in the BPSF group, fixation type was not a significant predictor on regression. CONCLUSIONS: ALIF with UPSF relative to BPSF predicted decreased operative time but was not a significant predictor of postoperative outcomes. ALIF with UPSF can be considered to increase operative efficiency without compromising construct stability.

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