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1.
J Arthroplasty ; 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38889808

RESUMO

BACKGROUND: Using time-driven activity-based costing (TDABC), a novel cost calculation method that more accurately reflects true resource utilization in health care, we sought to compare the total facility costs across different body mass index (BMI) groups following total joint arthroplasty (TJA). METHODS: The study consisted of 13,806 TJAs (7,340 total knee arthroplasties [TKAs] and 6,466 total hip arthroplasties [THAs]) performed between 2019 and 2023. The TDABC data from an analytics platform was employed to depict total facility costs, comprising personnel and supply costs. For the analysis, patients were stratified into four BMI categories: <30, 30 to <35, 35 to <40, and ≥40. Multivariable regression was used to determine the independent effect of BMI on facility costs. RESULTS: When indexed to patients who had BMI <30, elevated BMI categories (30 to <35, 35 to <40, and ≥40) were associated with higher total personnel costs (TKA 1.03x versus 1.07x versus 1.13x, P < .001; THA 1.00x versus 1.08x versus 1.08x, P < .001), and total supply costs (TKA 1.01x versus 1.04x versus 1.04x, P < .001; THA 1.01x versus 1.02x versus 1.03x, P = .007). Total facility costs in TJAs were significantly greater in higher BMI categories (TKA 1.02x versus 1.05x versus 1.08x, P < .001; THA 1.01x versus 1.05x versus 1.05x, P < .001). Notably, when incorporating adjustments for demographics and comorbidities, BMI values of 35, 40, and 45 relative to BMI of 25, exhibit a significant association with a 2, 3, and 5% increase in total facility cost for TKAs and a 3, 5, and 7% increase for THAs. CONCLUSIONS: Using TDABC methodology, this study found that overall facility costs of TJAs increase with BMI. The present study provides patient-level cost insights, indicating the potential need for reassessment of physician compensation models in this population. Further studies may facilitate the development of risk-adjusted procedural codes and compensation models for public and private payors. LEVEL OF EVIDENCE: Level IV, economic and decision analyses.

2.
Osteoporos Int ; 35(6): 951-969, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38300316

RESUMO

Fracture liaison services (FLS) have been proven clinically effective and cost-effective in preventing subsequent fractures among patients with an existing fragility fracture. Little is known about their monetary benefits such as their return on investment (ROI). This systematic review aimed to investigate the ROI of FLS and identify the FLS characteristics with better ROI. Studies on the cost-effectiveness of FLS published between January 2000 and December 2022 were searched from MEDLINE, EMBASE, PubMed, and Cochrane Central. Two independent reviewers conducted study selection and data extraction. ROI was calculated based on the difference between monetary benefits and FLS costs divided by the FLS costs. Subgroup analysis of ROI was performed across FLS types and FLS design details. A total of 23 FLS were included in this review. The majority of them were targeting patients aged over 50 years having fractures without identified sites. The mean ROI of these FLS was 10.49 (with a median ROI of 7.57), and 86.96% of FLS had positive ROI. FLS making treatment recommendations yielded the highest ROI (with a mean ROI of 18.39 and a median of 13.60). Incorporating primary care providers (with a mean ROI of 16.04 and a median of 13.20) or having them as program leaders (with a mean ROI of 12.07 and a median of 12.07) has demonstrated a high ROI. FLS for specific fracture sites had great monetary return. Intensive FLS such as type A and B FLS programs had higher ROI than non-intensive type C and D FLS. This review revealed a 10.49-fold monetary return of FLS. Identified characteristics contributing to greater economic return informed value-for-money FLS designs. Findings highlight the importance of FLS and the feasibility of expanding their contribution in mitigating the economic burden of osteoporotic fracture and are conducive to the promotion of FLS internationally.


Assuntos
Análise Custo-Benefício , Fraturas por Osteoporose , Humanos , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Prevenção Secundária/organização & administração , Prevenção Secundária/economia
3.
JBJS Rev ; 11(10)2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37793005

RESUMO

The evaluation and treatment of adolescents and young adults with hip pain has seen tremendous growth over the past 20 years. Labral tears are well established as a common cause of hip pain but often occur because of underlying bony abnormalities. Femoroacetabular impingement (FAI) and acetabular dysplasia are now well-established causes of hip osteoarthritis and are increasingly treated in the prearthritic stage in hopes of improving symptoms and prolonging the longevity of the native hip. Beyond FAI and acetabular dysplasia, this patient population can present with a complex and variable group of underlying conditions that need to be taken into account. Expertise in the conservative management of this population, including physical therapy, is valuable to maximize the success. Preoperative, surgical, and postoperative decision-making and care in this population is complex and evolving. A comprehensive, multidisciplinary approach to the care of this patient population has been used for over 20 years by our institution with great success. The purpose of this article is to review the "team-based approach" necessary for successful management of the spectrum of adolescent and young adult hip disorders.


Assuntos
Impacto Femoroacetabular , Luxação Congênita de Quadril , Luxação do Quadril , Adulto Jovem , Adolescente , Humanos , Articulação do Quadril/cirurgia , Impacto Femoroacetabular/cirurgia , Quadril , Artralgia/etiologia
4.
Zookeys ; 1179: 313-352, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745621

RESUMO

The exploration of unsurveyed areas in southern Thailand discovered two new karst-adapted species, Cyrtodactylussungaiupesp. nov. and Cyrtodactyluswangkhramensissp. nov., from Thung Wa and La-ngu Districts, Satun Province, respectively. These new species are members of the C.pulchellus group that occur along the Thai-Malay Peninsula. The new species can be distinguished from all other congeners by their key morphological characters and genetic divergence. Morphologically, Cyrtodactylussungaiupesp. nov. and Cyrtodactyluswangkhramensissp. nov. can be diagnosed from other members by having a combination of differences in body size; degree of dorsal tuberculation; absence of tubercles on ventral surfaces; number of ventral scales, paravertebral tubercles and femoroprecloacal pores in males only; deep precloacal groove only in males; absence of a scattered pattern of white dorsal tubercles; number of dark body bands; and the extent of caudal tubercles on an original tail. Although the two species are sister taxa and have nearly identical morphologies, they are considered to be different species, based on a relatively high uncorrected pairwise genetic divergence of the mitochondrial ND2 gene (6.59-6.89%), statistically significant univariate and multivariate morphological differences (PERMANOVA and ANOVA) and diagnostic characteristics of caudal tuberculation on the original tail. Moreover, Cyrtodactylussungaiupesp. nov. and Cyrtodactyluswangkhramensissp. nov. are currently restricted to their karstic type localities which may serve as a geographic barrier to dispersal and gene flow.

6.
Diabet Med ; 40(11): e15184, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37467116

RESUMO

AIM: To determine low-density lipoprotein cholesterol (LDL-C) screening frequency and levels, and factors associated with elevated LDL-C, in Australasian youth with type 1 diabetes (T1D). METHODS: Data were extracted from the Australasian Diabetes Data Network (ADDN), a prospective clinical quality registry, on all T1D healthcare visits attended by young people aged 16-25 years (with T1D duration of >1 year) between January 2011 and December 2020. The primary outcomes were elevated LDL-C > 2.6 mmol/L (100 mg/dL) and threshold for treatment: >3.4 mmol/L (130 mg/dL), according to consensus guidelines. Multivariable Generalised Estimated Equations (GEE) were used to examine factors associated with elevated LDL-C across all visits. RESULTS: A cohort of 6338 young people (52.6% men) were identified, of whom 1603 (25.3%) had ≥1 LDL-C measurement documented. At last measurement, mean age, age at T1D diagnosis and T1D duration were 18.3 ± 2.4, 8.8 ± 4.5 and 8.9 ± 4.8 years, respectively. LDL-C was elevated in 737 (46.0%) and at the treatment threshold in 250 (15.6%). In multivariable GEE elevated LDL-C continuously was associated with older age (OR = 0.07; 0.01-0.13, p = 0.02), female sex (OR = 0.31; 0.18-0.43; p < 0.001), higher HbA1c (OR = 0.04; 0.01-0.08; p = 0.01) and having an elevated BMI (OR = 0.17, 0.06-0.39, p < 0.001). CONCLUSIONS: LDL-C screening and levels are suboptimal in this cohort, increasing future cardiovascular complication risk. There is an urgent need to understand how healthcare services can support improved screening and management of dyslipidaemia in this population.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 1 , Dislipidemias , Masculino , Humanos , Adolescente , Feminino , Adulto Jovem , Diabetes Mellitus Tipo 1/tratamento farmacológico , LDL-Colesterol , Estudos Prospectivos , Dislipidemias/epidemiologia , Dislipidemias/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia
7.
J Pediatr Orthop ; 43(6): 379-385, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-36952253

RESUMO

PURPOSE: Patients with X-linked hypophosphatemic rickets (XLH) often develop coronal plane knee deformities despite medical treatment. Hemiepiphysiodesis is an effective way to correct coronal plane knee deformities in skeletally immature patients, but a full understanding of the rate of angular correction after hemiepiphysiodesis in XLH patients, compared with idiopathic cases is lacking. METHODS: We retrospectively reviewed charts of 24 XLH patients and 37 control patients without metabolic bone disease who underwent hemiepiphysiodesis. All patients were treated with standard-of-care medical therapy (SOC=active vitamin D and phosphate salt supplementation) in our clinical research center and had a minimum of 2-year follow-up after hemiepiphysiodesis. Demographic data as well as complications, repeat procedures, or recurrence/overcorrection were recorded. Standing lower extremity radiographs were evaluated before the surgical intervention and at subsequent hardware removal or skeletal maturity, whichever came first. Mean axis deviation, knee zone, mechanical lateral distal femoral angle (mLDFA), and medial proximal tibial angle were measured on each radiograph. The rate of angular correction was calculated as the change in mLDFA and medial proximal tibial angle over the duration of treatment. RESULTS: The magnitude of the initial deformity of the distal femur was greater in XLH patients as compared with control for varus (XLH mLDFA 97.7 +/- 4.9 vs. Control mLDFA 92.0 +/- 2.0 degrees) and valgus (XLH mLDFA 78.7 +/- 6.2 vs. Controls mLDFA 83.6 +/- 3.2 degrees). The rate of correction was dependent on age. When correcting for age, XLH patients corrected femoral deformity at a 15% to 36% slower rate than control patients for the mLDFA (>3 y growth remaining XLH 0.71 +/- 0.46 vs. control 0.84 +/- 0.27 degrees/month, <3 y growth remaining XLH 0.37 +/- 0.33 vs. control 0.58 +/- 0.41 degrees/month). No significant differences were seen in the rate of proximal tibia correction. XLH patients were less likely to end treatment in zone 1 (55.0% XLH vs. 77.8% control). XLH patients had longer treatment times than controls (19.5 +/- 10.7 vs. 12.6 +/- 7.0 mu, P value <0.001), a higher average number of secondary procedures than controls (1.33 +/- 1.44 vs. 0.62 +/- 0.92 number of procedures), a higher rate of overcorrection than controls (29.2% vs. 5.4%), and a higher rate of subsequent corrective osteotomy than controls (37.5% vs. 8.1%). There was no significant difference in the rate of complications between groups (8.3% vs. 5.4%). CONCLUSIONS: Patients with XLH undergoing hemiepiphysiodesis have a 15% to 36% slower rate of femoral deformity correction that results in longer treatment times, a higher likelihood to undergo more secondary procedures, and a lower likelihood to reach neutral mechanical alignment. SIGNIFICANCE: This study provides important information to guide the timing and treatment of patients with XLH and coronal plane knee deformities. In addition, results from this study can be educational for families and patients with respect to anticipated treatment times, success rates of the procedure, complication rate, and likelihood of needing repeat procedures.


Assuntos
Raquitismo Hipofosfatêmico Familiar , Humanos , Raquitismo Hipofosfatêmico Familiar/cirurgia , Estudos Retrospectivos , Tíbia/cirurgia , Extremidade Inferior , Fêmur/cirurgia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Articulação do Joelho/anormalidades
8.
Clin Exp Med ; 23(2): 333-346, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35377095

RESUMO

The role of platelet function indices-platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), immature platelet fraction (IPF), and platelet mass index (PMI)-in psoriasis is uncertain. This systematic review and meta-analysis aimed to evaluate the association of these platelet biomarkers with both presence and severity of psoriasis. We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library from inception to November 2021. To evaluate the association of platelet function indices and psoriasis, we recorded mean differences (MD) and 95% confidence intervals (CI) as well as correlation coefficients (r) for each included study, and generated summary estimates using random-effects inverse-variance modelling. We screened 1,079 unique studies, and included 33 studies with 6724 patients in the quantitative analyses. Compared with controls, patients with psoriasis had higher PLT (MD 12.86 × 109/L, 95% CI 6.34-19.39, p < 0.001), MPV (MD 0.61fL, 95% CI 0.31-0.92, p < 0.001), and PCT (MD 0.05%, 95% CI 0.01-0.09, p = 0.010), but similar PDW (MD 0.16%, 95% CI -0.46-0.79, p = 0.610). Psoriasis Area and Severity Index (PASI) was weakly correlated with PLT (r 0.17, 95% CI 0.06-0.28, p = 0.003), MPV (r 0.36, 95% CI 0.22-0.49, p < 0.001), and PDW (r 0.17, 95% CI 0.08-0.26, p < 0.001). Study numbers were insufficient to judge the relationship of IPF and PMI with psoriasis presence, or PCT, IPF, and PMI with psoriasis severity. In summary, PLT, MPV, and PCT are significantly elevated in patients with psoriasis, and PLT, MPV, and PDW are weakly correlated with PASI. Future studies are needed to evaluate the independent diagnostic and prognostic potentials of these biomarkers in patients with psoriasis.


Assuntos
Plaquetas , Volume Plaquetário Médio , Humanos , Contagem de Plaquetas , Prognóstico , Biomarcadores
9.
J Orthop Trauma ; 36(12): 643, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36399677

RESUMO

OBJECTIVES: To examine the effectiveness and complication rates in age- and size-appropriate patients with either stable or unstable fracture patterns treated with elastic stable intramedullary nailing (ESIN). DESIGN: Retrospective case series. SETTING: Academic tertiary care children's hospital. PATIENTS/PARTICIPANTS: This was a consecutive series of 106 preadolescent children with femoral shaft fractures. The mean age of the patients was 8.0 years (range, 4.0-16.0 years). INTERVENTION: All children were treated by retrograde ESIN. MAIN OUTCOME MEASURES: Fractures were categorized as either length stable or unstable. Length stability and complications were assessed. A subset of patients with final full-length, standing x-rays was also evaluated. RESULTS: We analyzed 63 stable and 43 length unstable fractures. The mean age and weight of the patients with stable and unstable fractures were similar. There was no difference in complication rates between groups (χ2(1) = 0.00, P = 0.99). There was no difference (t(96.93) = 0.53, P = 0.59) in femoral shaft length change. Leg length discrepancies as assessed by full-length standing radiographs at follow-up were similar (χ2(2) = 1.52, P = 0.47). CONCLUSIONS: Preadolescent children younger than 10 years do not experience increased complications after ESIN of length unstable femur fractures [odds ratio (OR) = 1.68 (0.18-16.87), P = 0.65]. Length unstable femur fractures are not at increased risk of more complications [OR = 0.90 (0.26-2.92), P = 0.87], early femoral shortening [OR = (0.42-2.02), P = 0.85], or leg length discrepancy [OR = (0.13-1.56), P = 0.21] when treated with ESIN. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for complete description of levels of evidence.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Humanos , Criança , Pré-Escolar , Adolescente , Fixação Intramedular de Fraturas/efeitos adversos , Estudos Retrospectivos , Diáfises/cirurgia , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Fêmur/cirurgia , Desigualdade de Membros Inferiores/etiologia
10.
J Pediatr Orthop ; 42(10): 539-544, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36037440

RESUMO

BACKGROUND: After treatment with in situ stabilization, slipped capital femoral epiphysis (SCFE) patients have variable degrees of deformity that can contribute to femoroacetabular impingement (FAI). To evaluate the severity of residual deformity most physicians currently use biplanar radiographs of an anteroposterior pelvis which profiles the lateral head-neck deformity and a frog lateral view which profiles the anterior head-neck deformity. However, the assessment of FAI morphology commonly relies on the 45-degree Dunn view to profile the anterolateral head-neck junction where FAI deformity is maximal. Therefore, the purpose of this study was to compare the magnitude of residual SCFE deformity detected on the frog lateral radiograph to the 45-degree Dunn radiograph. METHODS: A retrospective review of radiographic images of 50 hips (47 patients) diagnosed with SCFE at a single academic institution from 2014 to 2018 was performed. The group included 25 hips evaluated postoperatively after fixation (Group 1) and 25 hips presenting with residual symptomatic SCFE deformity after previous pinning (Group 2). The alpha angle was assessed on both the 45-degree Dunn and frog lateral views for comparison. The modified Southwick slip angle was assessed on the frog lateral view only as a measure of SCFE severity. RESULTS: The Dunn view showed the maximal residual SCFE deformity as measured by the alpha angle in 88% (44/50) of cases. Overall, the mean alpha angle (70.7 degree vs. 60.1 degree, P <0.001) was significantly larger on the Dunn view as compared with frog lateral. Subgroup analysis showed a larger alpha angle on Dunn view compared with frog lateral in both immediate postoperative and residual SCFE deformities as well: Group 1 (69.5 degree vs. 60.9 degree, P <0.001) and Group 2 (71.9 degree vs. 59.3 degree, P <0.001). CONCLUSION: In patients with SCFE, the maximal residual deformity of the proximal femur can typically be seen on the 45-degree Dunn view, rather than on the frog lateral view. Our findings suggest the 45-degree Dunn view may be beneficial part of the postoperative assessment of SCFEs to quantify the true maximal deformity present. LEVEL OF EVIDENCE: Level IV.


Assuntos
Impacto Femoroacetabular , Escorregamento das Epífises Proximais do Fêmur , Progressão da Doença , Impacto Femoroacetabular/diagnóstico por imagem , Impacto Femoroacetabular/cirurgia , Fêmur/cirurgia , Humanos , Radiografia , Estudos Retrospectivos , Escorregamento das Epífises Proximais do Fêmur/cirurgia
12.
J Hip Preserv Surg ; 9(2): 126-133, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35854803

RESUMO

Complex deformities of the hip requiring intra-articular and proximal femoral correction are challenging with regard to surgical access and complication risk. Combined surgical dislocation and proximal femoral osteotomy (SD/PFO) is a surgical strategy that provides unrestricted access to the joint with the capability for adjunctive PFO. Although providing excellent surgical access, concerns over a potentially high risk of postoperative complications remain, and published information on the safety of this technique remain scarce. In this study, we defined the early complication profile of combined surgery across 48 hips with a variety of complex deformities using a standardized, validated complication grading scheme for hip preservation surgery. Patients were mean age 19.1 years 13-33 years and 60% had previous surgery. At the early mean follow-up of 2.9 years, considerable improvement was seen across all outcome scores. Major complications (Grade III or higher) occurred at a rate of 4.2% (n = 2). Both were osteotomy non-unions, and both were treated successfully with revision PFO and bone grafting at mean 1.1 years. To our knowledge, the current series of combined SD-PFO surgeries represents the largest to date for which detailed complication data have been reported. Given the complexity of these disorders, a major complication rate of 4.2% is acceptable. Our complication rates were comparable to those reported for isolated SD and PFO procedures. These rates did not vary significantly across morphologic variants or patient-specific characteristics. Additionally, our complication risk profile is consistent with previous, smaller reports, which supports the generalizability of these results among appropriately experienced surgeons.

13.
Proc Natl Acad Sci U S A ; 119(29): e2121036119, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858351

RESUMO

Many processes of biological diversification can simultaneously affect multiple evolutionary lineages. Examples include multiple members of a gene family diverging when a region of a chromosome is duplicated, multiple viral strains diverging at a "super-spreading" event, and a geological event fragmenting whole communities of species. It is difficult to test for patterns of shared divergences predicted by such processes because all phylogenetic methods assume that lineages diverge independently. We introduce a Bayesian phylogenetic approach to relax the assumption of independent, bifurcating divergences by expanding the space of topologies to include trees with shared and multifurcating divergences. This allows us to jointly infer phylogenetic relationships, divergence times, and patterns of divergences predicted by processes of diversification that affect multiple evolutionary lineages simultaneously or lead to more than two descendant lineages. Using simulations, we find that the method accurately infers shared and multifurcating divergence events when they occur and performs as well as current phylogenetic methods when divergences are independent and bifurcating. We apply our approach to genomic data from two genera of geckos from across the Philippines to test if past changes to the islands' landscape caused bursts of speciation. Unlike previous analyses restricted to only pairs of gecko populations, we find evidence for patterns of shared divergences. By generalizing the space of phylogenetic trees in a way that is independent from the likelihood model, our approach opens many avenues for future research into processes of diversification across the life sciences.


Assuntos
Biodiversidade , Lagartos , Filogenia , Animais , Teorema de Bayes , Genoma , Lagartos/classificação , Lagartos/genética
14.
Adv Child Dev Behav ; 62: 191-230, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35249682

RESUMO

Audio-visual recording and location tracking produce enormous quantities of digital data with which researchers can document children's everyday interactions in naturalistic settings and assessment contexts. Machine learning and other computational approaches can produce replicable, automated measurements of these big behavioral data. The economies of scale afforded by repeated automated measurements offer a potent approach to investigating linkages between real-time behavior and developmental change. In our work, automated measurement of audio from child-worn recorders-which quantify the frequency of child and adult speech and index its phonemic complexity-are paired with ultrawide radio tracking of children's location and interpersonal orientation. Applications of objective measurement indicate the influence of adult behavior in both expert ratings of attachment behavior and ratings of autism severity, suggesting the role of dyadic factors in these "child" assessments. In the preschool classroom, location/orientation measures provide data-driven measures of children's social contact, fertile ground for vocal interactions. Both the velocity of children's movement toward one another and their social contact with one another evidence homophily: children with autism spectrum disorder, other developmental disabilities, and typically developing children were more likely to interact with children in the same group even in inclusive preschool classrooms designed to promote interchange between all children. In the vocal domain, the frequency of peer speech and the phonemic complexity of teacher speech predict the frequency and phonemic complexity of children's own speech over multiple timescales. Moreover, children's own speech predicts their assessed language abilities across disability groups, suggesting how everyday interactions facilitate development.


Assuntos
Transtorno do Espectro Autista , Adulto , Pré-Escolar , Humanos , Grupo Associado , Instituições Acadêmicas
15.
PeerJ ; 10: e13153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35341041

RESUMO

The gekkonid genus Cyrtodactylus is the third largest vertebrate genus on the planet with well over 300 species that range across at least eight biogeographic regions from South Asia to Melanesia. The ecological and morphological plasticity within the genus, has contributed to its ability to disperse across ephemeral seaways, river systems, basins, land bridges, and mountain ranges-followed by in situ diversification within specific geographic areas. Ancestral ranges were reconstructed on a mitochondrial phylogeny with 346 described and undescribed species from which it was inferred that Cyrtodactylus evolved in a proto-Himalaya region during the early Eocene. From there, it dispersed to what is currently Indoburma and Indochina during the mid-Eocene-the latter becoming the first major center of origin for the remainder of the genus that seeded dispersals to the Indian subcontinent, Papua, and Sundaland. Sundaland became a second major center of radiation during the Oligocene and gave rise to a large number of species that radiated further within Sundaland and dispersed to Wallacea, the Philippines, and back to Indochina. One Papuan lineage dispersed west to recolonize and radiate in Sundaland. Currently, Indochina and Sundaland still harbor the vast majority of species of Cyrtodactylus.


Assuntos
Lagartos , Animais , Filogenia , Filipinas , Indochina , Ásia Meridional
16.
Nucleic Acids Res ; 50(3): 1620-1638, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35104878

RESUMO

The life of RNA polymerase II (RNAPII) transcripts is shaped by the dynamic formation of mutually exclusive ribonucleoprotein complexes (RNPs) that direct transcript biogenesis and turnover. A key regulator of RNA metabolism in the nucleus is the scaffold protein ARS2 (arsenic resistance protein 2), bound to the cap binding complex (CBC). We report here that alternative splicing of ARS2's intron 5, generates cytoplasmic isoforms that lack 270 amino acids from the N-terminal of the protein and are functionally distinct from nuclear ARS2. Switching of ARS2 isoforms within the CBC in the cytoplasm has dramatic functional consequences, changing ARS2 from a NMD inhibitor to a NMD promoter that enhances the binding of UPF1 to NCBP1 and ERF1, favouring SURF complex formation, SMG7 recruitment and transcript degradation. ARS2 isoform exchange is also relevant during arsenic stress, where cytoplasmic ARS2 promotes a global response to arsenic in a CBC-independent manner. We propose that ARS2 isoform switching promotes the proper recruitment of RNP complexes during NMD and the cellular response to arsenic stress. The existence of non-redundant ARS2 isoforms is relevant for cell homeostasis, and stress response.


Assuntos
Arsênio , Degradação do RNAm Mediada por Códon sem Sentido , Arsênio/metabolismo , Núcleo Celular/metabolismo , Degradação do RNAm Mediada por Códon sem Sentido/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Helicases/genética , RNA Polimerase II/genética , RNA Polimerase II/metabolismo
17.
J Bone Joint Surg Am ; 104(9): 780-789, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35196296

RESUMO

BACKGROUND: Residual Legg-Calvé-Perthes (LCP) deformities represent one of the most challenging disorders in hip reconstructive surgery. In complex cases, both instability (acetabular dysplasia) and multifocal femoroacetabular impingement (FAI) (proximal femoral deformities) require correction. We assessed intermediate-term patient-reported outcome measures, radiographic correction, complications, and survivorship for combined surgical dislocation (SD) and periacetabular osteotomy (PAO) for the treatment of complex LCP deformities. METHODS: A retrospective cohort study was performed on 31 hips with complex LCP deformities undergoing combined SD and PAO for concurrent instability and FAI. Treatment included femoral head reshaping, trochanteric advancement and relative femoral neck lengthening, management of intra-articular lesions, and PAO. Twenty-seven hips (87%) had a minimum follow-up of 5 years. The mean age was 19.8 years, 56% of patients were female, and 44% of patients had undergone a previous surgical procedure. RESULTS: At a mean of 8.4 years, 85% of hips (23 of 27) remained preserved (no conversion to total hip arthroplasty). The survivorship estimates were 93% at 5 years and 85% at 10 years. The median (and interquartile range) increased from 64 points (55, 67 points) to 92 points (70, 97 points) (p < 0.001) for the modified Harris hip score (mHHS) and from 60 points (45, 75 points) to 86 points (75, 100 points) (p = 0.001) for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Symptoms (mHHS < 70 points) were reported for an additional 19% of hips (n = 5) at the final follow-up. The University of California Los Angeles (UCLA) activity score increased from a median of 8 points (6, 10 points) to 9 points (7, 10 points) (p = 0.207). Structural correction included mean improvement (and standard deviation) of 15.3° ± 7.6° for acetabular inclination, 20.7° ± 10.8° for the lateral center-edge angle, 23.4° ± 16.3° for the anterior center-edge angle, and 18 ± 10 mm for trochanteric height (p < 0.001 for all). Complications occurred in 2 hips (7%), including 1 deep wound infection and 1 superficial wound infection. There was 1 reoperation due to complication, but there were no nerve palsies, thromboembolic events, fractures, or nonunions. CONCLUSIONS: At an intermediate follow-up of combined SD and PAO for complex LCP deformities, 85% of hips were preserved. This procedure provides reliable deformity correction, major pain relief, improved function, and acceptable complication and failure rates. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Impacto Femoroacetabular , Infecção dos Ferimentos , Acetábulo/patologia , Adulto , Feminino , Articulação do Quadril/cirurgia , Humanos , Masculino , Osteotomia/métodos , Dor , Estudos Retrospectivos , Resultado do Tratamento , Infecção dos Ferimentos/patologia , Adulto Jovem
18.
Pharmaceutics ; 14(2)2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35213967

RESUMO

One of the major issues in current radiotherapy (RT) is the associated normal tissue toxicity. Enhancement of the RT effect with novel radiosensitizers can address this need. In this study, gold nanoparticles (GNPs) and bleomycin (BLM) were used as a unique combination of radiosensitizers. GNPs offer a two-fold promise as a delivery vehicle for BLM and as a radiosensitizing agent. In this study, GNPs were functionalized and complexed with BLM using a gold-thiol bond (denoted GNP-BLM). Our results show that there was a 40% and 10% decrease in cell growth with GNP-BLM vs. free BLM for the MIA PaCa-2 and PC-3 cell lines, respectively. Testing the GNP-BLM platform with RT showed an 84% and 13% reduction in cell growth in MIA PaCa-2 cells treated with GNP-BLM and GNPs, respectively. Similar results were seen with PC-3 cells. The efficacy of this approach was verified by mapping DNA double-strand breaks (DSBs) as well. Therefore, this proposed incorporation of nanomedicine with RT is promising in achieving a significantly higher therapeutic ratio which is necessary to make a paradigm change to the current clinical approach.

19.
Mol Ecol Resour ; 22(3): 1100-1119, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34569723

RESUMO

Despite the prevalence of high-throughput sequencing in phylogenetics, many relationships remain difficult to resolve because of conflicting signal among genomic regions. Selection of different types of molecular markers from different genomic regions is required to overcome these challenges. For evolutionary studies in frogs, we introduce the publicly available FrogCap suite of genomic resources, which is a large collection of ~15,000 markers that unifies previous genetic sequencing efforts. FrogCap is designed to be modular, such that subsets of markers and SNPs can be selected based on the desired phylogenetic scale. FrogCap uses a variety of marker types that include exons and introns, ultraconserved elements, and previously sequenced Sanger markers, which span up to 10,000 bp in alignment lengths; in addition, we demonstrate potential for SNP-based analyses. We tested FrogCap using 121 samples distributed across five phylogenetic scales, comparing probes designed using a consensus- or exemplar genome-based approach. Using the consensus design is more resilient to issues with sensitivity, specificity, and missing data than picking an exemplar genome sequence. We also tested the impact of different bait kit sizes (20,020 vs. 40,040) on depth of coverage and found triple the depth for the 20,020 bait  kit. We observed sequence capture success (i.e., missing data, sequenced markers/bases, marker length, and informative sites) across phylogenetic scales. The incorporation of different marker types is effective for deep phylogenetic relationships and shallow population genetics studies. Having demonstrated FrogCap's utility and modularity, we conclude that these new resources are efficacious for high-throughput sequencing projects across variable timescales.


Assuntos
Anuros , Genética Populacional , Animais , Anuros/genética , Genoma , Genômica , Filogenia
20.
Poult Sci ; 101(2): 101409, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34953376

RESUMO

Salmonella Infantis has been the etiological agent of numerous foodborne outbreaks of nontyphoidal Salmonella. Consequently, there is an emergent need to mitigate Salmonella Infantis among poultry. Thus, this study evaluated the efficacy of cetylpyridinium chloride (CPC) versus peroxyacetic acid (PAA), on bone-in, skin-on chicken thighs for the reduction of Salmonella and changes in the microbiota. Exactly 100 skin-on, bone-in chicken thighs (2 trials, 0 and 24 h, k = 5, n = 5, N = 50) were inoculated with 108 CFU/mL of a nalidixic acid resistant strain of S. Infantis for an attachment of 106 CFU/g. Thighs were treated with 20 s part dips (350 mL): a no inoculum, no treatment control (NINTC); no treatment control (NTC); tap water (TW); TW+CPC; TW+PAA. Following treatment, thighs were rinsed in 150 mL of nBPW, and rinsates were collected. Rinsates were spot plated for Salmonella and aerobic bacteria (APC). Log10 transformed counts were analyzed using a mixed-effects model (random effect = trial) with means separated using Tukey's HSD (P ≤ 0.05). The genomic DNA of rinsates was extracted, and the 16S rDNA was sequenced on an Illumina MiSeq. Microbiota data were analyzed using QIIME2, with data considered significant at P ≤ 0.05 (main effects) and Q≤0.05 (pairwise differences). Treatment × time interactions were observed for both Salmonella and APC (P < 0.05). The treatment of thighs with PAA and CPC reduced Salmonella and APC in respect to the controls. Numerically, thighs treated with CPC had less Salmonella (4.29 log10CFU/g) and less APC (4.56 log10CFU/g) at 24 h than all other treatments (P > 0.05). Differences in diversity metrics were not consistently observed between treatments; however, in trial 2, the NTC treated thighs were different than those treated with CPC (P < 0.05; Q < 0.05). In both trials, ANCOM, the analysis of microbiome compositional profiles, revealed shifts at both the phylum and order levels with thighs being different in the relative abundances of Proteobacteria (P < 0.05). In conclusion, treatment of skin-on poultry parts with CPC may reduce the risk of foodborne outbreaks caused by Salmonella Infantis.


Assuntos
Galinhas , Microbiota , Animais , Cetilpiridínio/farmacologia , Microbiologia de Alimentos , Salmonella , Coxa da Perna
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