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1.
Childs Nerv Syst ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904767

RESUMEN

BACKGROUND: Early surgical management of syndromic craniosynostosis varies widely between centers, with patients typically undergoing multiple intracranial procedures through childhood. This study evaluates the long-term impact of early posterior vault distraction osteogenesis (PVDO) versus conventional treatment paradigms on the number and timing of subsequent craniofacial procedures. METHODS: We retrospectively analyzed the longitudinal operative patterns of patients with syndromic craniosynostosis treated from 2000 to 2023 with greater than five years of follow-up. Outcomes of patients who underwent early PVDO and conventional vault reconstruction were compared. RESULTS: Fifty-five patients met the inclusion criteria (30 PVDO and 25 conventional). Age at initial vault surgery was similar between the PVDO and conventional cohorts (7.6 vs. 8.8 months), as were baseline craniometrics (p > 0.05). Multiple fronto-orbital advancement (FOA) procedures were performed in only 1/30 (3%) PVDO-treated patient versus 12/25 (48%) conventionally-treated patients (p < 0.001). Twelve (40%) PVDO-treated patients did not undergo FOA at all. Among patients with Apert and Crouzon syndromes, fewer PVDO-treated patients required FOA prior to midface surgery (33% vs. 92%, p = 0.004) or repeat FOA (6% vs. 50%, p = 0.005) compared to conventionally-treated patients. Among patients with Muenke and Saethre-Chotzen syndromes, a similar proportion of patients required FOA in the PVDO and conventional cohorts (91% vs. 100%, p = 0.353), though no PVDO-treated patients required repeat FOA (0% vs. 44%, p = 0.018). CONCLUSIONS: Early PVDO is associated with a reduction in the high burden of both FOA and, critically, revisionary frontal procedures which are commonly seen in conventionally-treated patients with syndromic craniosynostosis.

2.
Cleft Palate Craniofac J ; : 10556656241234804, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38425129

RESUMEN

OBJECTIVE: Identify and describe factors associated with retention and attrition of patients during longitudinal follow-up at multidisciplinary cleft clinic. DESIGN: Retrospective cohort study. SETTING: Single, tertiary care center. PATIENTS, PARTICIPANTS: Patients born between 1995 and 2007 with a diagnosis of cleft palate with or without cleft lip attending multidisciplinary cleft clinic. INTERVENTIONS: None tested, observational study. MAIN OUTCOME MEASURE(S): Age at last clinical appointment with a multidisciplinary cleft team provider. Attrition was defined as absence of an outpatient appointment following 15 years of age. RESULTS: Six hundred seventy-eight patients were included. The average age at last appointment across the entire cohort was 13.1 years (IQR 6.6-17.2). Patients who were Black (HR 1.60, 95% CI 1.10-2.32, p = 0.014) and other races (HR 1.90, 95% CI 1.22-2.98, p = 0.004) were more likely to be lost to follow-up compared to white patients. Publicly insured patients were more likely to experience attrition than those who were privately insured (HR 1.30, 95% CI 1.03-1.65, p = 0.030). Estimated income was not significantly associated with length of follow-up (p = 0.259). Those whose residence was in the fourth quartile of driving distance from our center experienced loss to follow-up significantly more than those who lived the closest (HR 2.04, 95% CI 1.50-2.78, p < 0.001). CONCLUSIONS: There is a high degree of follow-up attrition among patients with cleft lip and palate. Race, insurance status, and driving distance to our center were associated with attrition in a large, retrospective cohort of patients who have reached the age of cleft clinic graduation.

3.
Aesthet Surg J ; 44(4): 347-353, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-37930673

RESUMEN

Facial feminization surgery (FFS) is a form of gender-affirming care for the transgender population that is currently a highly debated topic both inside and outside of the medical community. Currently, a paucity of information is available in plastic surgery literature on ethical issues surrounding FFS. In this paper, we discuss 5 major ethical considerations for plastic surgeons with regard to FFS: (1) how society's changing view of gender has impacted the importance of FFS; (2) whether FFS is medically necessary and should be covered by insurance; (3) to what extent resources should be invested in removing barriers to access FFS; (4) how patient selection criteria should address the irreversibility of the procedure and age of consent; and (5) how femininity and beauty standards contribute to each other and whether they can be disentangled. This paper aims to analyze the arguments made for and against each of these 5 nuanced issues and to expand these debates from the theoretical to the practical by suggesting approaches for reconciliation.


Asunto(s)
Procedimientos de Cirugía Plástica , Cirugía Plástica , Personas Transgénero , Transexualidad , Masculino , Femenino , Humanos , Feminización/cirugía , Transexualidad/cirugía
4.
Medicina (Kaunas) ; 60(1)2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38256387

RESUMEN

Background and Objectives: Axillary tissue hypertrophy consists of ectopic breast tissue and occurs in up to six percent of women. Women complain of pain, interference with activity, and dissatisfaction with appearance. While it is recommended that accessory breast tissue be removed via surgical excision, there is lack of consensus on the best technique for the surgical management of axillary tissue hypertrophy. In this study, the senior authors (BC and NT) review outcomes and complications as they pertain to the surgical treatment of axillary tissue hypertrophy and axillary contouring. Materials and Methods: A retrospective review of all patients (n = 35), from two separate institutions, who presented with axillary tissue hypertrophy between December 2019 and August 2021 was conducted. All patients underwent a technique that included direct crescentic dermato-lipectomy and glandular excision with axillary crease obliteration. Tissue was sent for histological analysis after removal. During a six-month follow-up period, all patient outcomes were recorded. Results: The authors treated 35 women with axillary tissue hypertrophy. All patients complained of aesthetic deformity with significant discomfort leading to the desire for surgery. Histologically, all specimens contained benign breast and adipose tissue. Hypertrophic scarring, seroma, and axillary cording were noted complications. Conclusions: Detailed is the surgical management and optimal technique that can be used to treat both adipose and fibroglandular axillary tissue hypertrophy while simultaneously providing a favorable axillary aesthetic.


Asunto(s)
Abdominoplastia , Obesidad , Humanos , Femenino , Hipertrofia/cirugía , Tejido Adiposo , Estética
5.
Inj Prev ; 29(1): 91-100, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36600522

RESUMEN

CONTEXT: Costs related to criminal justice are an important component of the economic burden of injuries; such costs could include police involvement, judicial and corrections costs, among others. If the literature has sufficient information on the criminal justice costs related to injury, it could be added to existing estimates of the economic burden of injury. OBJECTIVE: To examine research on injury-related criminal justice costs, and what extent cost information is available by type of injury. DATA SOURCES: Medline, PsycINFO, Sociological Abstracts ProQuest, EconLit and National Criminal Justice Reference Service were searched from 1998 to 2021. DATA EXTRACTION: Preferred Reporting Items for Systematic reviews and Meta-Analyses was followed for data reporting. RESULTS: Overall, 29 studies reported criminal justice costs and the costs of crime vary considerably. CONCLUSIONS: This study illustrates possible touchpoints for cost inputs and outputs in the criminal justice pathway, providing a useful conceptualisation for better estimating criminal justice costs of injury in the future. However, better understanding of all criminal justice costs for injury-related crimes may provide justification for prevention efforts and potentially for groups who are disproportionately affected. Future research may focus on criminal justice cost estimates from injuries by demographics to better understand the impact these costs have on particular populations.


Asunto(s)
Crimen , Derecho Penal , Humanos , Policia
6.
Ann Plast Surg ; 90(6S Suppl 5): S607-S611, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36752405

RESUMEN

INTRODUCTION: Surgical advancements in breast reconstruction have allowed a shift toward optimizing patient-reported outcomes and efficiency measures. The enhanced recovery after surgery (ERAS) protocol has been instrumental in improving outcomes, but the effect of these protocols on health care spending has not been examined. This study aims to assess the effect of ERAS protocols on the length of hospital stay and costs associated with microsurgical breast reconstruction. METHODS: In 2018, the authors implemented an ERAS protocol for patients undergoing microsurgical breast reconstruction that included perioperative procedures involving patient education and care. Subjects included patients who underwent deep inferior epigastric perforator flap breast reconstruction at the authors' institution between 2016 and 2019. Data were gathered from the electronic medical record and the hospital system's finance department, and patients were divided into pre-ERAS and ERAS cohorts. A 2-sample t test was used for statistical analysis. RESULTS: The study included 269 patients with no statistically significant differences in demographic data between the cohorts. The average length of hospitalization was 3.46 days for the pre-ERAS group and 2.45 days for the ERAS group ( P = 0.000). In a linear regression, the ERAS protocol predicted a 1.04-day decrease in the length of stay ( P = 0.000). Overall, total direct cost decreased by 7.5% with the ERAS protocol. CONCLUSION: The rising cost of health care presents a challenge for providers to reduce the cost burden placed on our health system while providing the highest-quality care. This study demonstrates that the use of standardized ERAS protocols can achieve this 2-fold goal.


Asunto(s)
Recuperación Mejorada Después de la Cirugía , Costos de la Atención en Salud , Mamoplastia , Humanos , Costos y Análisis de Costo , Tiempo de Internación , Mamoplastia/economía , Procedimientos de Cirugía Plástica , Complicaciones Posoperatorias , Estudios Retrospectivos
7.
Artículo en Inglés | MEDLINE | ID: mdl-38062889

RESUMEN

BACKGROUND: The aim of many interventions used by speech and language therapists (SLTs) is to change behaviours related to communication and interaction. Parent-led language interventions for children in the early years (0-5 years) rely on SLTs supporting parents to change their behaviour in child-focused interactions to effect a change in the child's communication. Therapeutic techniques used by SLTs in parent-led language interventions are largely underspecified, impacting on intervention reporting, replication, trialling and development. The Behaviour Change Technique Taxonomy Version 1 (BCTTv1) offers a method of describing intervention techniques developed for use in public health interventions, but with several examples of its application to speech and language interventions. AIMS: To identify behaviour change techniques (BCTs) from the BCTTv1 occurring in parent-led language interventions for children in the early years. METHODS & PROCEDURES: A literature search identified relevant descriptions of parent-led language interventions. These were coded using the BCTTv1. A reliability check was carried out on 10% of the descriptions. To confirm the use of identified BCTs in clinical practice, results of the literature search were triangulated with an online survey of SLTs, and observations of SLTs delivering parent-led language intervention. OUTCOMES & RESULTS: A total of 84 papers containing descriptions of 45 interventions were coded; 62 SLTs responded to the survey and three SLTs were observed delivering parent-led language intervention. A total of 24 BCTs were identified in the literature search, replicated in the observations and verified by SLTs in the survey. BCTs were identified at two levels: Level 1 SLT implemented to change parent interactive behaviour; and Level 2 parent implemented to change child communicative behaviour. CONCLUSIONS & IMPLICATIONS: The BCTTv1 is a useful starting place for describing parent-led language interventions. With some additions and adjustments, BCTs identified in this study were immediately recognized by practitioners and can easily be adopted into practice. WHAT THIS PAPER ADDS: What is already known on this subject Techniques used in SLT interventions are often not clearly described. The BCTTv1 has been used to clarify technique descriptions with success in a small number of SLT disciplines, but not yet in parent-led language interventions for preschoola children. What this paper adds to the existing knowledge This paper constitutes the first research into quantifying the techniques used in parent-led language interventions using the BCTTv1. What are the potential or actual clinical implications of this work? This paper provides a clear list of techniques used by SLTs implementing interventions for preschool children, which can be immediately adopted and used in practice. It also highlights potential adjustments and gaps in the BCTTv1 in relation to SLT which can contribute to future iterations.

8.
Medicina (Kaunas) ; 59(12)2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38138173

RESUMEN

Facial Feminization Surgery (FFS) is a transformative surgical approach aimed at aligning the facial features of transgender women with their gender identity. Through a systematic analysis, this paper explores the clinical differences between male and female facial skeletons along with the craniofacial techniques employed in FFS for each region. The preoperative planning stage is highlighted, emphasizing the importance of virtual planning and AI morphing as valuable tools to be used to achieve surgical precision. Consideration is given to special circumstances, such as procedure sequencing for older patients and silicone removal. Clinical outcomes, through patient-reported outcome measures and AI-based gender-typing assessments, showcase the efficacy of FFS in achieving proper gender recognition and alleviating gender dysphoria. This comprehensive review not only offers valuable insights into the current state of knowledge regarding FFS but also emphasizes the potential of artificial intelligence in outcome evaluation and surgical planning to further advance patient care and satisfaction with FFS.


Asunto(s)
Feminización , Transexualidad , Humanos , Femenino , Masculino , Feminización/cirugía , Inteligencia Artificial , Identidad de Género , Cara/cirugía , Transexualidad/cirugía
9.
Am J Hum Genet ; 105(1): 108-121, 2019 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-31204009

RESUMEN

Pediatric acute liver failure (ALF) is life threatening with genetic, immunologic, and environmental etiologies. Approximately half of all cases remain unexplained. Recurrent ALF (RALF) in infants describes repeated episodes of severe liver injury with recovery of hepatic function between crises. We describe bi-allelic RINT1 alterations as the cause of a multisystem disorder including RALF and skeletal abnormalities. Three unrelated individuals with RALF onset ≤3 years of age have splice alterations at the same position (c.1333+1G>A or G>T) in trans with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del) in RINT1. ALF episodes are concomitant with fever/infection and not all individuals have complete normalization of liver function testing between episodes. Liver biopsies revealed nonspecific liver damage including fibrosis, steatosis, or mild increases in Kupffer cells. Skeletal imaging revealed abnormalities affecting the vertebrae and pelvis. Dermal fibroblasts showed splice-variant mediated skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay. Fibroblasts also revealed decreased RINT1 protein, abnormal Golgi morphology, and impaired autophagic flux compared to control. RINT1 interacts with NBAS, recently implicated in RALF, and UVRAG, to facilitate Golgi-to-ER retrograde vesicle transport. During nutrient depletion or infection, Golgi-to-ER transport is suppressed and autophagy is promoted through UVRAG regulation by mTOR. Aberrant autophagy has been associated with the development of similar skeletal abnormalities and also with liver disease, suggesting that disruption of these RINT1 functions may explain the liver and skeletal findings. Clarifying the pathomechanism underlying this gene-disease relationship may inform therapeutic opportunities.


Asunto(s)
Autofagia , Enfermedades del Desarrollo Óseo/etiología , Proteínas de Ciclo Celular/genética , Fibroblastos/patología , Fallo Hepático Agudo/etiología , Mutación , Edad de Inicio , Alelos , Secuencia de Aminoácidos , Enfermedades del Desarrollo Óseo/metabolismo , Enfermedades del Desarrollo Óseo/patología , Proteínas de Ciclo Celular/metabolismo , Niño , Preescolar , Femenino , Fibroblastos/metabolismo , Aparato de Golgi/metabolismo , Aparato de Golgi/patología , Humanos , Lactante , Fallo Hepático Agudo/metabolismo , Fallo Hepático Agudo/patología , Masculino , Linaje , Transporte de Proteínas , Recurrencia , Homología de Secuencia
10.
Genet Med ; 24(7): 1583-1591, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35499524

RESUMEN

PURPOSE: CTR9 is a subunit of the PAF1 complex (PAF1C) that plays a crucial role in transcription regulation by binding CTR9 to RNA polymerase II. It is involved in transcription-coupled histone modification through promoting H3K4 and H3K36 methylation. We describe the clinical and molecular studies in 13 probands, harboring likely pathogenic CTR9 missense variants, collected through GeneMatcher. METHODS: Exome sequencing was performed in all individuals. CTR9 variants were assessed through 3-dimensional modeling of the activated human transcription complex Pol II-DSIF-PAF-SPT6 and the PAF1/CTR9 complex. H3K4/H3K36 methylation analysis, mitophagy assessment based on tetramethylrhodamine ethyl ester perchlorate immunofluorescence, and RNA-sequencing in skin fibroblasts from 4 patients was performed. RESULTS: Common clinical findings were variable degrees of intellectual disability, hypotonia, joint hyperlaxity, speech delay, coordination problems, tremor, and autism spectrum disorder. Mild dysmorphism and cardiac anomalies were less frequent. For 11 CTR9 variants, de novo occurrence was shown. Three-dimensional modeling predicted a likely disruptive effect of the variants on local CTR9 structure and protein interaction. Additional studies in fibroblasts did not unveil the downstream functional consequences of the identified variants. CONCLUSION: We describe a neurodevelopmental disorder caused by (mainly) de novo variants in CTR9, likely affecting PAF1C function.


Asunto(s)
Trastorno del Espectro Autista , Discapacidad Intelectual , Trastornos del Neurodesarrollo , Fosfoproteínas , Factores de Transcripción , Regulación de la Expresión Génica , Heterocigoto , Humanos , Discapacidad Intelectual/genética , Trastornos del Neurodesarrollo/genética , Fosfoproteínas/genética , Factores de Transcripción/genética
11.
Inj Prev ; 28(5): 405-409, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35296543

RESUMEN

BACKGROUND: Quality-adjusted life years (QALYs) provide a means to compare injuries using a common measurement which allows quality of life and duration of life from an injury to be considered. A more comprehensive picture of the economic losses associated with injuries can be found when QALY estimates are combined with medical and work loss costs. This study provides estimates of QALY loss. METHODS: QALY loss estimates were assigned to records in the 2018 National Electronic Injury Surveillance System - All Injury Program. QALY estimates by body region and nature of injury were assigned using a combination of previous research methods. Injuries were rated on six dimensions, which identify a set of discrete qualitative impairments. Additionally, a seventh dimension, work-related disability, was included. QALY loss estimates were produced by intent and mechanism, for all emergency department-treated cases, by two disposition groups. RESULTS: Lifetime QALY losses ranged from 0.0004 to 0.388 for treated and released injuries, and from 0.031 to 3.905 for hospitalised injuries. The 1-year monetary value of QALY losses ranged from $136 to $437 000 among both treated and released and hospitalised injuries. The lifetime monetary value of QALY losses for hospitalised injuries ranged from $16 000 to $2.1 million. CONCLUSIONS: These estimates provide information to improve knowledge about the comprehensive economic burden of injuries; direct cost elements that can be measured through financial transactions do not capture the full cost of an injury. Comprehensive assessment of the long-term cost of injuries, including quality of life losses, is critical to accurately estimate the economic burden of injuries.


Asunto(s)
Servicio de Urgencia en Hospital , Calidad de Vida , Análisis Costo-Beneficio , Humanos , Intención , Años de Vida Ajustados por Calidad de Vida
12.
J Reconstr Microsurg ; 38(9): 721-726, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35292953

RESUMEN

BACKGROUND: Accurate assessment of regional lymph node basins is critical for oncological management of breast cancer. The internal mammary lymph node (IMLN) basin directly drains the medial pole of the breast, but biopsy is not commonly performed. While the axillary sentinel lymph node sample remains the standard of care, the majority of patients who have been found to have a positive IMLN biopsy have simultaneously had negative axillary sentinel lymph nodes. This study prospectively examines routine IMLN biopsy during microsurgical breast reconstruction. METHODS: An IRB-approved study of routine IMLN biopsies in 270 consecutive patients who underwent microsurgical breast reconstruction was performed from July 1, 2018, to June 1, 2021. Recorded data included unilateral or bilateral breast reconstruction, unilateral or bilateral IMLN sampling, patient demographics, disease stage, and pathologic findings of IMLN. RESULTS: The majority of patients, 240 of 270 patients (88.9%), had bilateral reconstruction. Overall, 5 out of 270 (1.9%) patients had positive IMLN; one of these patients had positive axillary sentinel lymph nodes. The IMLN biopsy results in two of the five patients affected the clinical course as they were upstaged and required chemoradiation. CONCLUSION: Direct visualization of the internal mammary lymph nodes during dissection of the recipient vessels for microsurgical breast reconstruction allows for convenient sampling, with minimal donor site morbidity and enhances the therapeutic management of patients in whom nodal involvement is present. As such, the authors recommend IMLN sampling.


Asunto(s)
Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Estudios Prospectivos , Biopsia del Ganglio Linfático Centinela/métodos , Metástasis Linfática/patología , Estudios Retrospectivos , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Mamoplastia/métodos , Axila/cirugía , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Escisión del Ganglio Linfático , Estadificación de Neoplasias
13.
J Am Chem Soc ; 143(9): 3348-3358, 2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33625838

RESUMEN

The desolvated (3,24)-connected metal-organic framework (MOF) material, MFM-160a, [Cu3(L)(H2O)3] [H6L = 1,3,5-triazine-2,4,6-tris(aminophenyl-4-isophthalic acid)], exhibits excellent high-pressure uptake of CO2 (110 wt% at 20 bar, 298 K) and highly selective separation of C2 hydrocarbons from CH4 at 1 bar pressure. Henry's law selectivities of 79:1 for C2H2:CH4 and 70:1 for C2H4:CH4 at 298 K are observed, consistent with ideal adsorption solution theory (IAST) predictions. Significantly, MFM-160a shows a selectivity of 16:1 for C2H2:CO2. Solid-state 2H NMR spectroscopic studies on partially deuterated MFM-160-d12 confirm an ultra-low barrier (∼2 kJ mol-1) to rotation of the phenyl group in the activated MOF and a rotation rate 5 orders of magnitude slower than usually observed for solid-state materials (1.4 × 106 Hz cf. 1011-1013 Hz). Upon introduction of CO2 or C2H2 into desolvated MFM-160a, this rate of rotation was found to increase with increasing gas pressure, a phenomenon attributed to the weakening of an intramolecular hydrogen bond in the triazine-containing linker upon gas binding. DFT calculations of binding energies and interactions of CO2 and C2H2 around the triazine core are entirely consistent with the 2H NMR spectroscopic observations.

14.
Genet Med ; 23(3): 498-507, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33144682

RESUMEN

PURPOSE: Exome sequencing often identifies pathogenic genetic variants in patients with undiagnosed diseases. Nevertheless, frequent findings of variants of uncertain significance necessitate additional efforts to establish causality before reaching a conclusive diagnosis. To provide comprehensive genomic testing to patients with undiagnosed disease, we established an Individualized Medicine Clinic, which offered clinical exome testing and included a Translational Omics Program (TOP) that provided variant curation, research activities, or research exome sequencing. METHODS: From 2012 to 2018, 1101 unselected patients with undiagnosed diseases received exome testing. Outcomes were reviewed to assess impact of the TOP and patient characteristics on diagnostic rates through descriptive and multivariate analyses. RESULTS: The overall diagnostic yield was 24.9% (274 of 1101 patients), with 174 (15.8% of 1101) diagnosed on the basis of clinical exome sequencing alone. Four hundred twenty-three patients with nondiagnostic or without access to clinical exome sequencing were evaluated by the TOP, with 100 (9% of 1101) patients receiving a diagnosis, accounting for 36.5% of the diagnostic yield. The identification of a genetic diagnosis was influenced by the age at time of testing and the disease phenotype of the patient. CONCLUSION: Integration of translational research activities into clinical practice of a tertiary medical center can significantly increase the diagnostic yield of patients with undiagnosed disease.


Asunto(s)
Exoma , Enfermedades no Diagnosticadas , Exoma/genética , Pruebas Genéticas , Humanos , Fenotipo , Investigación Biomédica Traslacional , Secuenciación del Exoma
15.
Epilepsia ; 62(7): e103-e109, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34041744

RESUMEN

CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow-up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.


Asunto(s)
Discapacidades del Desarrollo/genética , Epilepsia Generalizada/genética , Adolescente , Adulto , Edad de Inicio , Niño , Preescolar , Discapacidades del Desarrollo/fisiopatología , Epilepsias Mioclónicas/diagnóstico , Epilepsias Mioclónicas/etiología , Epilepsias Mioclónicas/genética , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/etiología , Exoma/genética , Femenino , Variación Genética , Humanos , Lactante , Discapacidad Intelectual/etiología , Discapacidad Intelectual/genética , Masculino , Mutación/genética , Fenotipo , Estado Epiléptico/diagnóstico , Estado Epiléptico/etiología , Estado Epiléptico/genética , Adulto Joven
16.
Langmuir ; 37(30): 9170-9178, 2021 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-34292730

RESUMEN

The peptide angiotensin-converting enzyme inhibitors captopril and lisinopril are unexpectedly shown to exhibit critical aggregation concentration (CAC) behavior through measurements of surface tension, electrical conductivity, and dye probe fluorescence. These three measurements provide similar values for the CAC, and there is also evidence from circular dichroism spectroscopy for a possible conformational change in the peptides at the same concentration. Cryogenic transmission electron microscopy indicates the formation of micelle-like aggregates above the CAC, which can thus be considered a critical micelle concentration, and the formation of aggregates with a hydrodynamic radius of ∼6-7 nm is also evidenced by dynamic light scattering. We also used synchrotron radiation X-ray diffraction to determine the single-crystal structure of captopril and lisinopril. Our results improve the accuracy of previous data reported in the literature, obtained using conventional X-ray sources. We also studied the structure of aqueous solutions containing captopril or lisinopril at high concentrations. The aggregation may be driven by intermolecular interactions between the proline moiety of captopril molecules or between the phenylalanine moiety of lisinopril molecules.


Asunto(s)
Captopril , Lisinopril , Inhibidores de la Enzima Convertidora de Angiotensina
17.
MMWR Morb Mortal Wkly Rep ; 70(48): 1655-1659, 2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34855726

RESUMEN

Unintentional and violence-related injuries, including suicide, homicide, overdoses, motor vehicle crashes, and falls, were among the top 10 causes of death for all age groups in the United States and caused nearly 27 million nonfatal emergency department (ED) visits in 2019.*,† CDC estimated the economic cost of injuries that occurred in 2019 by assigning costs for medical care, work loss, value of statistical life, and quality of life losses to injury records from the CDC's Web-based Injury Statistics Query and Reporting System (WISQARS).§ In 2019, the economic cost of injury was $4.2 trillion, including $327 billion in medical care, $69 billion in work loss, and $3.8 trillion in value of statistical life and quality of life losses. More than one half of this cost ($2.4 trillion) was among working-aged adults (aged 25-64 years). Individual persons, families, organizations, communities, and policymakers can use targeted proven strategies to prevent injuries and violence. Resources for best practices for preventing injuries and violence are available online from CDC's National Center for Injury Prevention and Control.¶.


Asunto(s)
Costo de Enfermedad , Heridas y Lesiones/economía , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología , Heridas y Lesiones/epidemiología , Adulto Joven
18.
Global Health ; 17(1): 18, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33522937

RESUMEN

BACKGROUND: The success of the Sustainable Development Goals (SDGs) is predicated on multisectoral collaboration (MSC), and the COVID-19 pandemic makes it more urgent to learn how this can be done better. Complex challenges facing countries, such as COVID-19, cut across health, education, environment, financial and other sectors. Addressing these challenges requires the range of responsible sectors and intersecting services - across health, education, social and financial protection, economic development, law enforcement, among others - transform the way they work together towards shared goals. While the necessity of MSC is recognized, research is needed to understand how sectors collaborate, inform how to do so more efficiently, effectively and equitably, and ascertain similarities and differences across contexts. To answer these questions and inform practice, research to strengthen the evidence-base on MSC is critical. METHODS: This paper draws on a 12-country study series on MSC for health and sustainable development, in the context of the health and rights of women, children and adolescents. It is written by core members of the research coordination and country teams. Issues were analyzed during the study period through 'real-time' discussions and structured reporting, as well as through literature reviews and retrospective feedback and analysis at the end of the study. RESULTS: We identify four considerations that are unique to MSC research which will be of interest to other researchers, in the context of COVID-19 and beyond: 1) use theoretical frameworks to frame research questions as relevant to all sectors and to facilitate theoretical generalizability and evolution; 2) specifically incorporate sectoral analysis into MSC research methods; 3) develop a core set of research questions, using mixed methods and contextual adaptations as needed, with agreement on criteria for research rigor; and 4) identify shared indicators of success and failure across sectors to assess MSCs. CONCLUSION: In responding to COVID-19 it is evident that effective MSC is an urgent priority. It enables partners from diverse sectors to effectively convene to do more together than alone. Our findings have practical relevance for achieving this objective and contribute to the growing literature on partnerships and collaboration. We must seize the opportunity here to identify remaining knowledge gaps on how diverse sectors can work together efficiently and effectively in different settings to accelerate progress towards achieving shared goals.


Asunto(s)
Salud Global , Colaboración Intersectorial , Investigación , Desarrollo Sostenible , COVID-19/prevención & control , Países en Desarrollo , Humanos
19.
Inj Prev ; 27(2): 111-117, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32366517

RESUMEN

OBJECTIVE: To estimate the average lost work productivity due to non-fatal injuries in the USA comprehensively by injury type. METHODS: The attributable average number and value of lost work days in the year following non-fatal emergency department (ED)-treated injuries were estimated by injury mechanism (eg, fall) and body region (eg, head and neck) among individuals age 18-64 with employer health insurance injured 1 October 2014 through 30 September 2015 as reported in MarketScan medical claims and Health and Productivity Management databases. Workplace, short-term disability and workers' compensation absences were assessed. Multivariable regression models compared lost work days among injury patients and matched controls during the year following injured patients' ED visit, controlling for demographic, clinical and health insurance factors. Lost work days were valued using an average US daily market production estimate. Costs are 2015 USD. RESULTS: The 1-year per-person average number and value of lost work days due to all types of non-fatal injuries combined were approximately 11 days and US$1590. The range by injury mechanism was 1.5 days (US$210) for bites and stings to 44.1 days (US$6196) for motorcycle injuries. The range by body region was 4.0 days (US$567) for other head, face and neck injuries to 19.8 days (US$2787) for traumatic brain injuries. CONCLUSIONS AND RELEVANCE: Injuries are costly and preventable. Accurate estimates of attributable lost work productivity are important to monitor the economic burden of injuries and help to prioritise cost-effective public health prevention activities.


Asunto(s)
Indemnización para Trabajadores , Lugar de Trabajo , Adolescente , Adulto , Bases de Datos Factuales , Humanos , Seguro de Salud , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto Joven
20.
Chemistry ; 26(14): 2984, 2020 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-32031299

RESUMEN

Invited for the cover of this issue is the group of Michael D. Ward at the University of Warwick. The image depicts structures of the host cage containing one guest or two guests. Read the full text of the article at 10.1002/chem.201905499.

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