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1.
J Med Entomol ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691677

RESUMEN

We conducted surveys of New Jersey mosquito control and public health agencies to determine their willingness and ability to expand or create and maintain publicly funded tick and tick-borne disease (T/TBD) management programs. Nearly all (86%) of 21 county mosquito control agencies (MCAs) completed the survey, while only 25% of the 102 health departments (HDs) responded, probably reflecting traditional agency responsibilities. Although few of either group had formal programs, many were engaged in T/TBD-related activities. Many MCAs rated their ability to assume T/TBD responsibilities as high or moderate, while most HDs rated their capabilities as low. With the exceptions of lack of sustainable funding and possible legal constraints, the groups differed regarding perceived barriers to program creation and maintenance. Both groups envisioned comprehensive programs emphasizing public education, but program priorities differed between the groups. MCAs were willing to include most program activities, while HDs felt that some activities should be the responsibility of other agencies. MCAs were generally more familiar than HDs with tick control methods and while both groups would include control in a comprehensive program, both would limit control to public lands. Estimated program costs varied widely, probably reflecting responding agency size and complexity of envisioned programs. These results in a state with a system of existing agencies staffed by highly competent professionals suggest that more than simply additional funding (e.g., established guidelines for tick control and surveillance) is needed to create a network of practice necessary to address the growing incidence of TBD.

2.
Orthop Traumatol Surg Res ; : 103844, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38395349

RESUMEN

INTRODUCTION: Visual clarity in arthroscopic rotator cuff repair is essential to reduce the operative time and for efficiency of repair. Tranexamic acid (TXA) in open shoulder surgery has been shown to reduce blood loss but its use in shoulder arthroscopy for rotator cuff repair for improved clarity is not understood. The purpose of this SR is to determine the effect of TXA and epinephrine on visual clarity in shoulder arthroscopy for rotator cuff repair. HYPOTHESIS: We hypothesise that visual clarity should improve in those that have TXA compared to those who do not receive TXA. METHODS: A review of the online databases MEDLINE and Embase was conducted on 8th October 2022 according to PRISMA guidelines. The review was registered prospectively in the PROSPERO database. Randomised clinical trials reporting visual clarity and/or, operative time, volume of irrigation fluid used and mean arterial pressure were included. The studies were appraised using the CONSORT tool. RESULTS: Seven studies met eligible criteria, all of which were double-blinded RCTs. Five studies reported no difference in visual clarity between TXA vs. saline, while two reported a significant improvement with TXA. Pooling of data showed that visual clarity was significantly better in the TXA group vs. saline, on a standardised 10-point Likert scale (mean difference 0.73 points, p=0.03). However, the use of epinephrine was reported in two studies and its administration offered significantly better visual clarity than TXA (mean difference 0.9 points, p=0.02). There was no significant difference with TXA use in MAP (mean difference 1.2mmHg, p=0.14), operative time (mean difference 6.8minutes, p=0.11), irrigation volume used (mean difference 0.2L, p=0.88), or postoperative pain (mean difference 3.89 on a 0-100 VAS, p=0.34). CONCLUSION: The use of TXA in shoulder arthroscopy has shown to have significantly improved visual clarity in comparison to saline irrigation alone. This may not necessarily result in a significant clinical difference and may not translate to significantly less operative time or postoperative pain score. Furthermore, epinephrine use alone offers significantly better clarity than TXA. There may not be an added benefit to give both, but this area requires further research. LEVEL OF EVIDENCE: II; systematic review.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38281678

RESUMEN

BACKGROUND: Management of displaced distal clavicle fractures remains a topic of discussion because of notoriously high nonunion rates, but there is little documented in the literature as to what effect this may have on patient-reported function. The aim of this systematic review was to look at nonoperative management following displaced distal clavicle fractures to determine union rates, complications, and patient-reported outcome measures. METHODS: A review of the online databases MEDLINE and Embase was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Clinical studies that included a cohort of nonoperatively managed displaced distal clavicle fractures and reported on union rate, complications, and patient-reported functional scores were included. RESULTS: Eleven studies were eligible for inclusion (2 randomized controlled trials, 1 prospective noncomparative cohort study, 5 retrospective comparative cohort studies, and 3 case series) with a total of 779 patients included in this review. Average union rate was 63.2% (22.2%-94.4%) in nonoperatively managed patients, compared with 96.3% (87.9%-100%) in operatively managed patients. The Constant-Murley score and Disabilities of the Arm, Shoulder, and Hand questionnaire were the most frequently used outcome measure tools. No study demonstrated any significant difference in any outcome measure when comparing nonoperative with operative treatment. Complication rate (including nonunion) in nonoperatively managed patients was 45.1%, with 11.1% requiring delayed surgery. Average complication rate in the operatively managed groups was 41.2%, with 40.1% requiring a second operation. CONCLUSION: Nonoperative management of displaced distal clavicle fractures results in higher nonunion rates, but shoulder function remains excellent, and risk of complications and delayed surgery are low. Decision making must take into account patient factors and expectations to provide high-quality, individualized care.

4.
Orthop Traumatol Surg Res ; : 103750, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37949394

RESUMEN

INTRODUCTION: Pyrocarbon promises to be an optimal material choice for radial head arthroplasty (RHA) due to an elastic modulus comparable to the radial diaphysis and thus providing higher biocompatibility. Primary objective was to determine the complications and revision rates related to the usage of these prostheses. The secondary objective was to assess the clinical and radiological outcomes of Pyrocarbon RHAs. HYPOTHESIS: Pyrocarbon RHAs have good clinical and radiological outcomes with low complications and revisions. METHODS: Ovid MEDLINE and Embase databases were used to search for studies on outcomes and complications of the RHAs using Pyrocarbon radial head prostheses. The systematic review was designed in accordance with the PRISMA guidelines and included studies were appraised using the MINORS tool. Complications and RHA revision rates were assessed. Functional outcomes were reviewed using PROMs (like MEPI, DASH and BMS), post-op range of motion (using goniometer) and grip strength (using the dynamometer). Postoperative radiological outcomes like peri-prosthetic lucency, radial neck osteolysis, radio-capitellar congruence, capitellar erosion, overstuffing/understuffing and osteoarthritis were reported using radiographs. RESULTS: A total of 12 studies cumulatively reporting 353 patients who underwent Pyrocarbon RHAs were included in the review. The mean age of patients across the studies ranged from 47 to 54 years of which 50.5% were males. The majority of radial head replacements were done for acute trauma (87.5%) with the remainder done for arthritis (1.7%) and trauma sequelae (10.8%). Mean follow-up period in the selected studies ranged from 18 to 110 months with minimum follow-up across all studies being 12 months. Modular Pyrocarbon (MoPyC, Tornier™) was the implant of choice in ten studies while two studies used the Ascension Pyrocarbon radial head (Ascension Orthopaedics™). Ten studies demonstrated mean MEPI ranging from 75.5 to 96. Mean extension deficit ranged from 6 to 19 degrees, mean flexion from 120 to 140 degrees, mean pronation from 71 to 87 degrees and mean supination from 63 to 85 degrees. Relative grip strength ranged from 69 to 96% of the contralateral limb. Revisions due to implant-related reasons (intra-prosthetic dissociation, prosthetic fracture, peri-prosthetic loosening, radio-capitellar subluxation and understuffed/overstuffed elbow) was 6.8% (24/353). Radial stress shielding and peri-prosthetic lucency was reported in 10 to 100% of patients across different studies but symptomatic implant loosening leading to revision remained rare (2%, 7/353). Radio-capitellar congruence was reported in 81% to 100% cases while capitellar erosion ranged from 0% to 89%. Pyrocarbon implants specific complications included head-neck intra-prosthetic decoupling (1.1%) and pyrocarbon head fractures (0.9%). In total, 5.7% cases underwent re-surgery due to non-RHA related reasons. DISCUSSION: The pyrocarbon RHA shows good functional outcome, range of motion and low revision rates. This aligns with the working hypothesis of this review. However, pyrocarbon radial head implants have implant-specific complications like pyrocarbon radial head fractures and intra-prosthetic decoupling between stem and head. Despite promising in vitro biomechanical properties, capitellar wear is still a common finding with pyrocarbon RHAs. Despite these factors, pyrocarbon radial head implants are a viable option for radial head arthroplasty. LEVEL OF EVIDENCE: II; Systematic review.

5.
Acta Orthop Belg ; 89(2): 362-368, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37924555

RESUMEN

The management of isolated radial neck and head fractures is controversial. Plate fixation and tripod fixation are two commonly employed techniques but risk damage to soft tissues and implant-related complications. Intramedullary fixation is commonly used in pediatric cases and reduces the potential drawbacks of open fixation. This systematic review aimed to analyze outcomes of intramedullary fixation in adults in terms of function, union, and complication rates. A systematic review of the literature was conducted following the PRISMA guidelines using Medline and EMBASE's online databases. The review was registered on the PROSPERO database. Studies were appraised using the Methodological Index for non-randomized studies (MINORS) tool. Seven studies were deemed eligible for inclusion (n=55). Mean ages of patients ranged from 31.3 to 44.2 years, and mean follow-up ranged from 9 to 86 months. The Mayo Elbow Performance score (MEPs) was reported in five case series (mean scores 81.8 -97.9) and the prevalence of excellent results ranged from 71% and 83%. Although 100% of fractures united, the pooled complication rate was 24% (range 0-50%). The most common complications were elbow stiffness (7%), superficial radial nerve neuropraxia (7%), malunion (5%), and AVN (1.8%). No study reported any patients requiring revision surgery. Intramedullary fixation for radial head and neck fractures appears to provide a reliable alternative treatment option in terms of union, range of motion, and functional outcomes. Further robust trials direct comparing against open fixation techniques are required.


Asunto(s)
Articulación del Codo , Fracturas Radiales de Cabeza y Cuello , Fracturas del Radio , Fracturas de la Columna Vertebral , Humanos , Adulto , Niño , Preescolar , Fracturas del Radio/cirugía , Resultado del Tratamiento , Radio (Anatomía) , Articulación del Codo/cirugía , Complicaciones Posoperatorias/epidemiología , Fijación Interna de Fracturas/métodos , Rango del Movimiento Articular , Estudios Retrospectivos
6.
Arthroscopy ; 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37890545

RESUMEN

PURPOSE: To compare the 2 Latarjet fixation techniques-screw fixation (SF) versus suture button (SB) -for clinical, biomechanical, and radiologic outcomes. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic and Meta-Analyses guidelines using MEDLINE and Embase databases and was prospectively registered on PROSPERO. Only comparative clinical and biomechanical studies of Latarjet with SF and SB were included. Studies were appraised using the Methodical Index for Non-Randomised Studies (MINORS) tool. RESULTS: Eleven studies met eligible criteria: 7 clinical studies (SB, n = 279; SF, n = 845) and 4 biomechanical. In total, 80.9% (SB) and 84.2% (SF) of patients were male. Follow-up ranged from 6 to 63.6 months. The overall recurrent instability rate for SB ranged from 0 to 8.3% and for SF ranged from 0 to 2.75%. Only one study demonstrated a greater recurrent instability rate with SB (P = .02). Overall SB complication rates ranged from 0 to 12.5% and SF ranged from 0 to 27%. Two studies reported greater complications and reoperations with SF related to hardware. Summary forest plots from 4 studies showed no significant difference in Walch Duplay score (mean difference, range -5.00 to 1.20 [95% confidence interval {CI} -12.13 to 8.56], I2 inconsistency = 0%), Rowe score (mean difference, range -2.00 to 4.00 [95% CI -7.37 to 7.66], I2 inconsistency = 45%), and VAS for pain (mean difference, range -0.10 to 0.60 [95% CI -0.72 to 1.33], I2 inconsistency = 0%). There was no statistically significant difference between SB and SF in the postoperative range of motion. Radiologically, there was no significant difference in graft positioning and union at final follow-up, but graft resorption was greater in SF (range 25.2%-47.6%) compared with SB (range 10.1%-18.5%). Biomechanical studies showed no significant difference in maximum load to failure (SB, range 184-266 N vs SF, range 148-288 N). CONCLUSIONS: Clinically, SB fixation demonstrated similar functional outcome and range of motion when compared with SF, with the potential benefit of lower rates of graft resorption and hardware-related complications. Biomechanically there was no difference in maximum load to failure. LEVEL OF EVIDENCE: Level III, cohort studies (all clinical studies were Level III cohort studies).

7.
J Infect Dis ; 228(Suppl 5): S337-S354, 2023 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-37669225

RESUMEN

The National Center for Advancing Translational Sciences (NCATS) Assay Guidance Manual (AGM) Workshop on 3D Tissue Models for Antiviral Drug Development, held virtually on 7-8 June 2022, provided comprehensive coverage of critical concepts intended to help scientists establish robust, reproducible, and scalable 3D tissue models to study viruses with pandemic potential. This workshop was organized by NCATS, the National Institute of Allergy and Infectious Diseases, and the Bill and Melinda Gates Foundation. During the workshop, scientific experts from academia, industry, and government provided an overview of 3D tissue models' utility and limitations, use of existing 3D tissue models for antiviral drug development, practical advice, best practices, and case studies about the application of available 3D tissue models to infectious disease modeling. This report includes a summary of each workshop session as well as a discussion of perspectives and challenges related to the use of 3D tissues in antiviral drug discovery.


Asunto(s)
Antivirales , Descubrimiento de Drogas , Antivirales/farmacología , Antivirales/uso terapéutico , Bioensayo
8.
J Ocul Pharmacol Ther ; 39(9): 600-610, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37677000

RESUMEN

Purpose: The melanocortin receptor pan-agonist PL9643, a potential therapy for ocular diseases, was investigated in a phase 2, 12-week study in patients with dry eye disease (DED). Methods: This was a placebo-controlled study evaluating efficacy and safety of thrice-daily PL9643. Placebo (vehicle) was similar to tears. Primary endpoints were intra-patient changes in inferior corneal fluorescein staining and ocular discomfort after 12 weeks. Secondary endpoints were changes in additional DED signs or symptoms. Multiple secondary endpoints were not adjusted for multiplicity. Patients with moderate or severe DED were analyzed in addition to the overall intent-to-treat (ITT) population. Results: In the ITT population (n = 160) the PL9643 group did not demonstrate significant treatment difference versus placebo at week 12/day 85 for the primary endpoints (P > 0.05). In patients with moderate or severe DED (n = 53), PL9643 treatment demonstrated either nominally significant (P < 0.05) or trending (P < 0.1) improvement over placebo in mean change from baseline at week 12/day 85 in several sign endpoints, including fluorescein staining in inferior, superior, corneal sum, and total sum regions; Lissamine Green staining in temporal, nasal, conjunctival sum, and total sum regions; and tear film breakup time. Conjunctival redness also showed (nonsignificant) improvement at week 12/day 85. There were no drug-related adverse events (AEs) and no drug-related discontinuations. Conclusions: PL9643 showed no significant efficacy for the ITT population; however, efficacy results across several signs and symptoms in the subpopulation of moderate to severe DED patients, the low number of ocular AEs, and no tolerability issues suggest that PL9643 shows promise as a therapeutic for DED. Clinical Trial Registration number: NCT04268069.


Asunto(s)
Síndromes de Ojo Seco , Humanos , Soluciones Oftálmicas/efectos adversos , Resultado del Tratamiento , Fluoresceína , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/diagnóstico , Córnea , Método Doble Ciego , Lágrimas
9.
Artículo en Inglés | MEDLINE | ID: mdl-37680762

RESUMEN

Several human pathogens vectored by the blacklegged tick (Ixodes scapularis Say; Acari: Ixodidae) are endemic in the state of New Jersey. Disease incidence data suggest that these conditions occur disproportionately in the northwestern portion of the state, including in the county of Hunterdon. We conducted active surveillance at three forested sites in Hunterdon County during 2020 and 2021, collecting 662 nymphal and adult I. scapularis. Ticks were tested for five pathogens by qPCR/qRT-PCR: Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, Borrelia miyamotoi, and Powassan virus (POWV) lineage 2. Over 2 years, 25.4% of nymphs and 58.4% of adults were found infected with at least one pathogen, with 10.6% of all ticks infected with more than one pathogen. We report substantial spatial and temporal variability of A. phagocytophilum and B. burgdorferi, with high relative abundance of the human-infective A. phagocytophilum variant Ap-ha. Notably, POWV was detected for the first time in Hunterdon, a county where human cases have not been reported. Based on comparisons with active surveillance initiatives in nearby counties, further investigation of non-entomological factors potentially influencing rates of tick-borne illness in Hunterdon is recommended.

10.
J Med Entomol ; 60(5): 1048-1060, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37540592

RESUMEN

Numerous studies have assessed the efficacy of environmentally based control methods to suppress populations of the blacklegged tick (Ixodes scapularis Say), but few of these estimated the cost of control. We estimated costs for a range of tick control methods (including habitat management, deer exclusion or population reduction, broadcast of acaricides, and use of host-targeted acaricides) implemented singly or in combination and applied to a model community comprising 320 residential properties and parklands. Using the high end for cost ranges, tick control based on a single method was estimated to have mean annual costs per household in the model community ranging from $132 for treating only forest ecotone with a broadcast synthetic acaricide to kill host-seeking ticks (or $404 for treating all residential forested habitat) to >$2,000 for deployment of bait boxes (SELECT TCS) across all residential tick habitat to treat rodents topically with acaricide to kill infesting ticks. Combining different sets of multiple methods in an integrated tick management program placed the annual cost between $508 and 3,192 annually per household in the model community, underscoring the disconnect between what people in Lyme disease endemic areas say they are willing to pay for tick control (not more than $100-150 annually) and the actual costs for tick control. Additional barriers to implementing community-based tick management programs within residential communities are discussed.


Asunto(s)
Acaricidas , Ciervos , Ixodes , Enfermedad de Lyme , Infestaciones por Garrapatas , Animales , Estudios de Factibilidad , Infestaciones por Garrapatas/prevención & control , Infestaciones por Garrapatas/veterinaria , Infestaciones por Garrapatas/epidemiología , Enfermedad de Lyme/epidemiología , Roedores , Control de Ácaros y Garrapatas/métodos
11.
Antiviral Res ; 217: 105678, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37494979

RESUMEN

The 36th International Conference on Antiviral Research (ICAR), sponsored by the International Society for Antiviral Research (ISAR), was held March 13-17, 2023, in Lyon, France, and concurrently through an interactive remote meeting platform. Here we provide a report summarizing the presentations at the 36th ICAR, including the ISAR speaker awards. We also detail special events, sessions, and additional awards conferred at the meeting. ICAR returned to in-person meetings in 2022, convening in Seattle, WA, USA. The 36th ICAR is the first in-person meeting of the society in Europe since the beginning of the COVID-19 pandemic, which restricted most events to virtual attendance to help mitigate the spread and subsequent public health impact of SARS-CoV-2. An exceptionally high number of registrants and record attendance at this year's ICAR, along with a vast array of demonstrable expertise in a variety of antiviral research-related fields, reflected a strong and growing antiviral research community committed to improving health outcomes from viral diseases, including SARS-CoV-2, and to future pandemic preparedness. This report highlights the breadth of expertise, quality of research, and notable advancements that were contributed by members of ISAR and other participants at the meeting. ICAR aims to continue to provide a platform for sharing information, fostering collaborations, and supporting trainees in the field of antiviral research. The 37th ICAR will be held in Gold Coast, Australia, May 20-24, 2024.


Asunto(s)
Antivirales , COVID-19 , Humanos , Antivirales/farmacología , Antivirales/uso terapéutico , Complejo Hierro-Dextran , Pandemias , SARS-CoV-2
12.
J Med Entomol ; 60(5): 1131-1135, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37341185

RESUMEN

We evaluated the relative effectiveness of the natural product acaricide Essentria IC3 and the entomopathogenic fungal acaricide BotaniGard ES to suppress host-seeking Ixodes scapularis Say and Amblyomma americanum (L.) nymphs when applied with low-pressure backpack and high-pressure sprayers. Essentria IC3 applied by backpack sprayer out-performed high-pressure applications, while the opposite was true for treatments with BotaniGard ES. We were unable to demonstrate consistently greater efficacy using high-pressure applications, and neither of the acaricides or application methods provided substantial (>90%) levels of control at 7 days postapplication.


Asunto(s)
Acaricidas , Ixodes , Animales , Amblyomma , Ninfa
13.
J Med Entomol ; 60(4): 842-846, 2023 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-37163525

RESUMEN

Lone star ticks (Amblyomma americanum L.) are expanding within the northeast United States, a region historically focused on Ixodes scapularis-transmitted diseases. In Monmouth County, NJ, the shift has been dramatic, and lone star ticks now vastly outnumber blacklegged ticks. As a result, there is an enhanced need to focus on the potential health risks of A. americanum-transmitted pathogens, such as the emerging Heartland (HRTV) and Bourbon (BRBV) viruses. We screened 1,205 nymphal lone star ticks for HRTV and BRBV using RT-qPCR assays and detected BRBV in 3 ticks collected in Monmouth County, NJ, in 2021. Additionally, we sequenced a complete BRBV genome from a single infected specimen, finding 99.4% identity with human pathogenic isolates from the eastern-central United States. Our results have important public health implications for a region only recently becoming aware of public health risks posed by lone star ticks. Of note, we report successful detection of viral RNA in samples that were stored and intended for DNA preservation, for example, kept in ethanol at room temperature, which may reduce barriers for public health agencies seeking to expand their tick testing to include viruses.


Asunto(s)
Ixodes , Ixodidae , Estados Unidos , Humanos , Animales , Amblyomma , New Jersey
14.
Small ; 19(35): e2207100, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37098606

RESUMEN

Materials are more easily damaged during accidents that involve rapid deformation. Here, a design strategy is described for electronic materials comprised of conducting polymers that defies this orthodox property, making their extensibility and toughness dynamically adaptive to deformation rates. This counterintuitive property is achieved through a morphology of interconnected nanoscopic core-shell micelles, where the chemical interactions are stronger within the shells than the cores. As a result, the interlinked shells retain material integrity under strain, while the rate of dissociation of the cores controls the extent of micelle elongation, which is a process that adapts to deformation rates. A prototype based on polyaniline shows a 7.5-fold increase in ultimate elongation and a 163-fold increase in toughness when deformed at increasing rates from 2.5 to 10 000% min-1 . This concept can be generalized to other conducting polymers and highly conductive composites to create "self-protective" soft electronic materials with enhanced durability under dynamic movement or deformation.

15.
Front Immunol ; 14: 1083333, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36891301

RESUMEN

Introduction: PL8177 is a potent and selective agonist of the melanocortin 1 receptor (MC1R). PL8177 has shown efficacy in reversing intestinal inflammation in a cannulated rat ulcerative colitis model. To facilitate oral delivery, a novel, polymer-encapsulated formulation of PL8177 was developed. This formulation was tested in 2 rat ulcerative colitis models and evaluated for distribution, in vivo, in rats, dogs, and humans. Methods: The rat models of colitis were induced by treatment with 2,4-dinitrobenzenesulfonic acid or dextran sulfate sodium. Single nuclei RNA sequencing of colon tissues was performed to characterize the mechanism of action. The distribution and concentration of PL8177 and the main metabolite within the GI tract after a single oral dose of PL8177 was investigated in rats and dogs. A phase 0 clinical study using a single microdose (70 µg) of [14C]-labeled PL8177 investigated the release of PL8177 in the colon of healthy men after oral administration. Results: Rats treated with 50 µg oral PL8177 demonstrated significantly lower macroscopic colon damage scores and improvement in colon weight, stool consistency, and fecal occult blood vs the vehicle without active drug. Histopathology analysis resulted in the maintenance of intact colon structure and barrier, reduced immune cell infiltration, and increased enterocytes with PL8177 treatment. Transcriptome data show that oral PL8177 50 µg treatment causes relative cell populations and key gene expressions levels to move closer to healthy controls. Compared with vehicle, treated colon samples show negative enrichment of immune marker genes and diverse immune-related pathways. In rats and dogs, orally administered PL8177 was detected at higher amounts in the colon vs upper GI tract. [14C]-PL8177 and the main metabolite were detected in the feces but not in the plasma and urine in humans. This suggests that the parent drug [14C]-PL8177 was released from the polymer formulation and metabolized within the GI tract, where it would be expected to exert its effect. Conclusion: Collectively, these findings support further research into the oral formulation of PL8177 as a possible therapeutic for GI inflammatory diseases in humans.


Asunto(s)
Colitis Ulcerosa , Colitis , Enfermedades Inflamatorias del Intestino , Humanos , Masculino , Ratas , Perros , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Receptor de Melanocortina Tipo 1 , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Colitis/inducido químicamente , Inflamación , alfa-MSH
16.
J Heart Lung Transplant ; 42(7): 908-916, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36964084

RESUMEN

BACKGROUND: Respiratory syncytial virus (RSV) infection in lung transplant recipients is associated with high morbidity. This study evaluated the RSV fusion inhibitor presatovir in RSV-infected lung transplant recipients. METHODS: In this international Phase 2b, randomized, double-blind, placebo-controlled trial (NCT02534350), adult lung transplant recipients with symptomatic confirmed RSV infection for ≤7 days received oral presatovir 200 mg on day 1 and 100 mg daily on days 2 to 14, or placebo (2:1), with follow-up through day 28. There were 2 coprimary endpoints: time-weighted average change in nasal RSV load from day 1 to 7, calculated from nasal swabs, in the full analysis set ([FAS]; all patients who received study drug and had quantifiable baseline nasal RSV load) and time-weighted average change in nasal RSV load from day 1 to 7 in the subset of patients with pretreatment symptom duration at the median or shorter of the FAS. Secondary endpoints were changes in respiratory infection symptoms assessed using the Influenza Patient-Reported Outcomes questionnaire and lung function measured by spirometry. RESULTS: Sixty-one patients were randomized, 40 received presatovir, 20 placebo, and 54 were included in efficacy analyses. Presatovir did not significantly improve the primary endpoint in the FAS (treatment difference [95% CI], 0.10 [-0.43, 0.63] log10 copies/ml; p = 0.72) or the shorter symptom-duration subgroup (-0.12 [-0.94, 0.69] log10 copies/ml; p = 0.76). Secondary endpoints were not different between presatovir and placebo groups. Presatovir was generally well tolerated. CONCLUSIONS: Presatovir treatment did not significantly improve change in nasal RSV load, symptoms, or lung function in lung transplant recipients.


Asunto(s)
Trasplante de Pulmón , Neumonía Viral , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Adulto , Humanos , Resultado del Tratamiento , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Neumonía Viral/complicaciones , Antivirales/uso terapéutico
18.
Inorg Chem ; 62(9): 3715-3721, 2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36812146

RESUMEN

Renewed interest in lanthanide contraction results from its possible effect on the properties and applications of Ln(III) compounds and the theory related to these issues. To understand this effect, it is important to know what is a normal dependence of the contraction on the number of 4f electrons, n. The normal trend is based on recent values of ionic radii that have a linear dependence on n for coordination numbers (CNs) of 6, 8, and 9. If the normal trend is not followed, then some other interactions in the system are affecting the extent of contraction. However, the suggestion that the variation is curved and fitted by a quadratic function has become popular in recent years. This report examines the Ln(III)-to-ligand atom distances for coordination compounds with CNs of 6-9 and the nitrides and phosphides. Least-squares fits to the linear and quadratic models are applied to all of the bond distances to determine when a quadratic model is justified. The result is that complex systems show a mixture of linear and quadratic dependencies when individual bond distances are considered and that the linear model is most common and representative of the true lanthanide contraction.

19.
Arch Orthop Trauma Surg ; 143(3): 1459-1477, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35178594

RESUMEN

BACKGROUND: It is well established that non-operative treatment of displaced distal clavicle fractures (DDCF) leads to a high non-union rate. A number of open surgical treatments in the past have shown good to excellent outcomes including shoulder function and union rate. Despite this there is no consensus on the outcome of open coraco-clavicular ligament reconstruction (CCLR). The aim of this systematic review was to assess the union rate, complications and shoulder function of open CCLR techniques in the treatment of DDCF. PATIENTS AND METHODS: A review of the online databases MEDLINE and Embase was conducted on 1 January 2021 according to PRISMA guidelines. The review was registered prospectively in the PROSPERO database. Clinical studies reporting union rate, complications and shoulder function were included. The studies were appraised using the Methodological Index for Non-Randomized Studies (MINORS) tool. RESULTS: The search strategy identified 18 studies eligible for inclusion with a total of 330 patients. These included 12 retrospective case series and 5 nonrandomized retrospective comparative studies and one RCT. All but one study reported on shoulder function, while all the studies reported on union rate and complications. The overall shoulder function was good to excellent using Constant-Murley score. The overall union rate was 97.6% and complication rate was 7.6%. CONCLUSION: Open CCLR for displaced distal clavicle fractures that have a disruption of CC ligament, is a reliable treatment with excellent union rate and good to excellent shoulder functional scores. LEVEL OF EVIDENCE: IV; Systematic review.


Asunto(s)
Clavícula , Fracturas Óseas , Humanos , Clavícula/cirugía , Estudios Retrospectivos , Fracturas Óseas/cirugía , Fijación Interna de Fracturas/métodos , Ligamentos , Resultado del Tratamiento , Placas Óseas
20.
Arch Orthop Trauma Surg ; 143(1): 329-352, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34988674

RESUMEN

INTRODUCTION: Non-operative treatment of displaced distal clavicle fractures results in high non-union and yet there is no consensus on superior treatment modality. While there are a number of different techniques available for fixation, hook plate (HP) has been used most commonly. A number of modern techniques, including superior plate (SP), have shown less complications but equivocal union rate and shoulder function. The aim of this systematic review and meta-analysis is to compare the outcome of HP fixation with superior plate in surgical fixation of displaced distal clavicle fractures. PATIENTS AND METHODS: A review of the online databases MEDLINE and Embase was conducted on 15 January 2021 according to PRISMA guidelines. The review was registered prospectively in the PROSPERO database. Clinical studies reporting union rate, complications and shoulder function were included. The studies were appraised using the Methodological Index for Non-Randomized Studies (MINORS) tool. RESULTS: The search strategy identified 42 studies eligible for inclusion with a total of 1,261 patients. These included 17 hook-plate case series (n = 573), 18 superior plate case series, of which 6 used SP alone (n = 223) and 12 SP and simultaneous CCLR case series (n = 189), and 7 studies comparing HP and SP (n = 276). The overall complication rate was significantly higher with HP when compared to SP [(32.7% vs 12.7%; OR 6.31 (95% CI: 2.67-14.91)]. The overall union rates in the case series appeared comparable in the current SR; HP 96.4%, SP 96.9% and SP with simultaneous CCLR 97.9%. Shoulder function was most commonly assessed using CM score and the mean ranged from 83.8 to 97.2 in HP, 89 to 98 in SP group and 90.6 to 97.6 in SP with CCLR. Meta-analysis of CM score failed to show a significant difference for HP versus SP (pooled weighted mean difference was 2.67 (95% CI: - 0.09 to 5.43) with a trend to favour SP fixation. CONCLUSION: The current review has demonstrated that HP, SP alone or with CCLR all offer excellent union rate and appear to provide comparative functional outcomes. However, HP is associated with significantly higher complication rates.


Asunto(s)
Fijación Interna de Fracturas , Fracturas Óseas , Humanos , Fijación Interna de Fracturas/métodos , Clavícula/cirugía , Fracturas Óseas/cirugía , Placas Óseas , Consenso , Resultado del Tratamiento , Estudios Retrospectivos
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