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1.
Proc Natl Acad Sci U S A ; 120(24): e2300189120, 2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37285393

RESUMEN

Using millions of observations compiled from the public administrative data of Taiwan, we find a surprising gender inequity in terms of real estate: Men own more land than women, and the annual rate of return (ROR) of men's land outperform women's by almost 1% per year. The latter finding of gender-based ROR difference is in sharp contrast to prior evidence that women outperform men in security investment, and also suggests a quantity-and-quality double jeopardy in female land ownership which, given the heavy weight of real estate in individual wealth, has important implications for wealth inequality among men and women. Our statistical analyses suggest that such a gender-based difference in land ROR cannot be attributed to individual-level factors such as liquidity preferences, risk attitudes, investment experience, and behavioral biases, as described in the literature. Rather, we hypothesize parental gender bias-a phenomenon that is still prevalent today-to be the key macrolevel factor. To test our hypothesis, we partition our observations into two groups: an experimental group in which parents can exercise gender discretion, and a control group in which parents cannot exercise such discretion. Our empirical evidence shows that the gender difference with respect to land ROR only exists in the experimental group. For many societies with long-lasting patriarchal traditions, our analysis provides a perspective to help explain gender differences in wealth distribution and social mobility.


Asunto(s)
Propiedad , Sexismo , Humanos , Femenino , Masculino , Factores Sexuales , Hombres , Inversiones en Salud
2.
Gene Ther ; 30(12): 792-800, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37696981

RESUMEN

Gene therapy approaches using adeno-associated viral vectors have been successfully tested in the equine post-traumatic osteoarthritis (PTOA) model. Owing to differences in the levels of transgene expression and adverse tissue reactions observed in published studies, we sought to identify a safe therapeutic dose of scAAVIL-1ra in an inflamed and injured joint that would result in improved functional outcomes without any adverse events. scAAVIL-1ra was delivered intra-articularly over a 100-fold range, and horses were evaluated throughout and at the end of the 10-week study. A dose-related increase in IL-1ra levels with a decrease in PGE2 levels was observed, with the peak IL-1ra concentration being observed 7 days post-treatment in all groups. Perivascular infiltration with mononuclear cells was observed within the synovial membrane of the joint treated with the highest viral dose of 5 × 1012 vg, but this was absent in the lower-dosed joints. The second-highest dose of scAAVeqIL-1ra 5 × 1011 vg demonstrated elevated IL-1ra levels without any cellular response in the synovium. Taken together, the data suggest that the 10-fold lower dose of 5 × 1011vg scAAVIL-1ra would be a safe therapeutic dose in an equine model of PTOA.


Asunto(s)
Proteína Antagonista del Receptor de Interleucina 1 , Osteoartritis , Animales , Caballos/genética , Proteína Antagonista del Receptor de Interleucina 1/genética , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Proyectos Piloto , Vectores Genéticos , Osteoartritis/terapia , Osteoartritis/metabolismo , Modelos Animales
3.
Ecol Lett ; 26(2): 219-231, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36604867

RESUMEN

Evolutionary success requires both production (acquisition of food, protection and warmth) and reproduction. We suggest that both may increase disproportionately as group size grows, reflecting 'increasing returns' or 'group augmentation benefits', raising fitness in groups that cooperate in production and limit reproduction to one or a few high fertility females supported by non-reproductives, with high reproductive skew. In our optimisation theory both Allee effects (when individual fitness increases with group size or density) and reproductive skew arise when increasing returns determine optimal group size and proportion of reproductive females. Depending on which of food or maternal time is more important for reproduction, evolutionary trajectories of lineages may (1) reach a boundary constraint where only one female reproduces in a period (as with African wild dogs) or (2) reach a boundary where all females reproduce during their lifetimes but only during an early life stage (human menopause) or a late life stage (birds with non-dispersing helpers), where stage length optimises the proportion of females that is reproductive at any time or (3) reach the intersection of these boundary constraints where a single reproductive female is fully specialised in reproduction (as with eusocial insects). We end with some testable hypotheses.


Asunto(s)
Insectos , Reproducción , Animales , Humanos , Femenino , Aves , Fertilidad , Evolución Biológica
4.
Opt Lett ; 48(2): 363-366, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36638458

RESUMEN

We present the operation of quantum cascade laser frequency combs in an external cavity configuration. Experimental observations show dependence of comb repetition rate and optical spectrum on the external cavity length. The low phase-noise comb regime is extended to a broader range of bias currents, enabling gapless frequency tuning of the comb modes. Dual-comb measurements also confirm improved comb stability in the presence of unwanted optical feedback when operating in an external cavity configuration. These observations indicate that aside from the continuing efforts to assure low and uniform dispersion characteristics of quantum cascade laser frequency combs, the proposed simple approach of adding a broadband external cavity can significantly enhance operation of sub-optimal devices for spectroscopic applications.

5.
BMC Public Health ; 23(1): 1643, 2023 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-37641018

RESUMEN

INTRODUCTION: Pre-exposure prophylaxis (PrEP) persistence among men who have sex with men (MSM) in real world clinical settings for HIV prevention is suboptimal. New longer-acting formulations of PrEP are becoming available, including injectables, subdermal implants, and other oral medications. These longer-acting formulations have the potential to improve retention among those who have challenges remaining adherent to daily oral PrEP. METHODS: We interviewed 49 MSM who had initiated but discontinued oral PrEP at three diverse clinics across the United States. We examined participants' perspectives about long-acting PrEP formulations and how long-acting options could affect PrEP use using thematic analysis. RESULTS: Participants were not very knowledgeable about long-acting formulations of PrEP but were open to learning about them and considering use. Participants were concerned about safety and efficacy of products given that they were still newer and/or in development. Finally, participants had clear preferences for oral pills, injectables, and then subdermal implants and were most interested in options that reduced the number of visits to the clinic. CONCLUSION: Long-acting formulations of PrEP are acceptable to MSM with suboptimal PrEP persistence and have the potential to improve PrEP persistence. However, many felt they needed more information on safety, efficacy, and use to consider these options. As these long-acting formulations are implemented, public health campaigns and clinical interventions to encourage may maximize uptake particularly among those who are not currently adherent to daily oral PrEP.


Asunto(s)
Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Masculino , Estados Unidos , Humanos , Homosexualidad Masculina , Instituciones de Atención Ambulatoria , Emociones
6.
Anal Chem ; 94(17): 6512-6520, 2022 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-35446548

RESUMEN

Label-free autofluorescence-detected photothermal mid-IR (AF-PTIR) microscopy is demonstrated experimentally and applied to test the distribution of active pharmaceutical ingredients (APIs) in a mixture containing representative pharmaceutical excipients. Two-photon excited UV-fluorescence (TPE-UVF) supports autofluorescence of native aromatic moieties using visible-light optics. Thermal modulation of the fluorescence quantum yield serves to report on infrared absorption, enabling infrared spectroscopy in the fingerprint region with a spatial resolution dictated by fluorescence. AF-PTIR provides high selectivity and sensitivity in image contrast for aromatic APIs, complementing broadly applicable optical photothermal IR (O-PTIR) microscopy based on photothermal modulation of refractive index/scattering. Mapping the API distribution is critical in designing processes for powdered dosage form manufacturing, with high spatial variance potentially producing variability in both delivered dosage and product efficacy. The ubiquity of aromatic moieties within API candidates suggests the viability of AF-PTIR in combination with O-PTIR to improve the confidence of chemical classification in spatially heterogeneous dosage forms.


Asunto(s)
Excipientes , Microscopía , Polvos , Espectrofotometría Infrarroja/métodos
7.
Osteoporos Int ; 33(3): 589-598, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34626209

RESUMEN

INTRODUCTION: Osteoporosis is a metabolic bone disease with low bone mineral density (BMD) and high incidence of vertebral fractures (VFs). Postmenopausal women with osteoporosis have decreased total fat and lean mass. This study aimed to investigate the associations between body composition and VF risk and explore the potential predictor of VF risk in postmenopausal women. METHODS: Enrolled 731 postmenopausal women were referred by various departments and outpatient clinics to assess vertebral status between October 2016 and November 2017. The main measures were total body lean mass, fat mass, and BMD. Patients were divided into osteopenia, osteoporosis, and normal groups based on T-scores. Logistic regression analyses were performed to evaluate associations between body composition parameters and VF. RESULTS: VF was significantly associated with increased age, lower height, and lighter weight in all participants, and higher BMI was observed in VF participants. Participants in the osteoporosis group were older and had lower height, weight, and BMD than those in normal and osteopenia groups. Femoral and total hip T-scores as well as T-scores for lumbar spine were significantly lower in participants with VF than in non-VF participants. Percentage of bone mass was also significantly lower in VF participants compared to that of non-VF participants. Women with increased BMD and lower bone mass had reduced odds for VF occurrence. Bone mass was significantly able to identify VF occurrence. CONCLUSIONS: Body composition analysis discerns differences in the bone status of postmenopausal women with and without VF. The cutoff value of the bone mass might be used effectively as an indicator of risk for VF occurrence.


Asunto(s)
Osteoporosis Posmenopáusica , Fracturas de la Columna Vertebral , Composición Corporal , Densidad Ósea , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/lesiones , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis Posmenopáusica/epidemiología , Posmenopausia , Factores de Riesgo , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiología
8.
BMC Infect Dis ; 22(1): 673, 2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-35931953

RESUMEN

BACKGROUND: Pre-exposure prophylaxis (PrEP) can significantly reduce HIV acquisition especially among communities with high HIV prevalence, including men who have sex with men (MSM). Much research has been finding suboptimal PrEP persistence; however, few studies examine factors that enhance PrEP persistence in real-world settings. METHODS: We interviewed 33 patients who identified as MSM at three different PrEP clinics in three regions of the U.S. (Northeast, South, Midwest). Participants were eligible if they took PrEP and had been retained in care for a minimum of 6 months. Interviews explored social, structural, clinic-level and behavioral factors that influencing PrEP persistence. RESULTS: Through thematic analysis we identified the following factors as promoting PrEP persistence: (1) navigation to reduce out-of-pocket costs of PrEP (structural), (2) social norms that support PrEP use (social), (3) access to LGBTQ + affirming medical providers (clinical), (4) medication as part of a daily routine (behavioral), and (5) facilitation of sexual health agency (belief). DISCUSSION: In this sample, persistence in PrEP care was associated with structural and social supports as well as a high level of perceived internal control over protecting their health by taking PrEP. Patients might benefit from increased access, LGBTQ + affirming medical providers, and communications that emphasize PrEP can promote sexual health.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Instituciones de Atención Ambulatoria , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Homosexualidad Masculina , Humanos , Masculino , Estados Unidos
9.
J Eur Acad Dermatol Venereol ; 36(3): 434-443, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34779063

RESUMEN

BACKGROUND: In JADE COMPARE, abrocitinib improved severity of atopic dermatitis (AD) and demonstrated rapid itch relief. OBJECTIVES: We examined clinically meaningful improvements in selected patient-reported outcomes (PROs). METHODS: JADE COMPARE was a multicentre, phase 3 randomized, double-blind, placebo-controlled trial. Adults with moderate-to-severe AD were randomized 2:2:2:1 to receive 16 weeks of oral abrocitinib 200 or 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo, with background topical therapy. PROs included Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Night Time Itch Scale (NTIS), Pruritus and Symptoms Assessment for Atopic Dermatitis, Patient Global Assessment, SCORing Atopic Dermatitis, and Hospital Anxiety and Depression Scale. RESULTS: At week 16, the proportion of patients achieving POEM scores <3 was 21.3% and 11.7% for 200 and 100 mg abrocitinib, 12.4% for dupilumab, and 4.8% for placebo (vs. abrocitinib, P < 0.0001 and P = 0.04). Proportion achieving ≥4-point improvement from baseline in NTIS severity was 64.3% and 52.4% for 200 and 100 mg abrocitinib, 54.0% for dupilumab, and 34.4% for placebo (vs. abrocitinib, P < 0.0001 and P = 0.007). Proportion achieving ≥4-point improvement from baseline in DLQI was 85.0% and 74.4% for 200 and 100 mg abrocitinib, 83.4% for dupilumab, and 59.7% for placebo (vs. abrocitinib, P < 0.0001 and P = 0.005). CONCLUSION: Significant improvements in PROs were demonstrated with both abrocitinib doses vs. placebo, and abrocitinib 200 mg provided numerically greater effects compared with dupilumab in patients with moderate-to-severe AD.


Asunto(s)
Dermatitis Atópica , Eccema , Adulto , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Método Doble Ciego , Eccema/tratamiento farmacológico , Humanos , Medición de Resultados Informados por el Paciente , Pirimidinas , Índice de Severidad de la Enfermedad , Sulfonamidas , Resultado del Tratamiento
10.
Proc Natl Acad Sci U S A ; 116(14): 6548-6553, 2019 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-30886101

RESUMEN

For a long time, social scientists have used correlations in social status, measured by such characteristics as schooling, income, or occupation, across family members to capture family resemblance in social status. In this study, we use millions of records from a public registry to estimate the wealth correlations among Taiwanese kinship members, from the closest parent-child pairing to the farthest kinship ties, with only 1/32 genetic relatedness. Based on this wealth correlation, we present a complete picture of economic similarity among kin members. These correlations give us a better grasp of the hitherto obscure Chinese family structure than that of mechanical genetic relatedness. We obtain statistical evidence to support the following hypotheses: Family members' wealth resemblance to male egos is stronger than to female egos, wealth correlations are larger along patrilineal lines than along matrilineal counterparts, wealthy families have larger correlations within the nuclear family members but smaller correlations outside it, and adopted children have weaker wealth resemblance with close relatives.


Asunto(s)
Ego , Renta , Relaciones Padres-Hijo , Sistema de Registros , Pueblo Asiatico , Femenino , Humanos , Masculino , Factores Socioeconómicos , Taiwán
11.
Osteoarthritis Cartilage ; 29(5): 687-696, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33610822

RESUMEN

OBJECTIVE: To address the need for early knee osteoarthritis (OA) markers by testing if longitudinal cartilage thickness changes are associated with specific biomechanical and biological measures acquired at a baseline test in asymptomatic aging subjects. DESIGN: Thirty-eight asymptomatic subjects over age 45 years were studied at baseline and at an average of 7-9 year follow-up. Gait mechanics and knee MRI were measured at baseline and MRI was obtained at follow-up to assess cartilage thickness changes. A subset of the subjects (n = 12) also had serum cartilage oligomeric matrix protein measured at baseline in response to a mechanical stimulus (30-min walk) (mCOMP). Baseline measures, including the knee extension (KEM), flexion (KFM), adduction (KAM) moments and mCOMP, were tested for associations with cartilage thickness changes in specific regions of the knee. RESULTS: Cartilage change in the full medial femoral condyle (p = 0.005) and external medial femoral region (p = 0.041) was negatively associated with larger early stance peak KEM. Similarly, cartilage change in the full medial femoral region (p = 0.009) and medial femoral external region (p = 0.043) was negatively associated with larger first peak KAM, while cartilage change in the anterior medial tibia was positively associated with larger first peak KAM (p = 0.003). Cartilage change in the anterior medial tibia was also significantly associated (p = 0.011) with mCOMP levels 5.5-h post-activity (percentage of pre-activity levels). CONCLUSIONS: Interactions found between gait, mechanically-stimulated serum biomarkers, and cartilage thickness in an at-risk aging asymptomatic population suggest the opportunity for early detection of OA with new approaches that bridge across disciplines and scales.


Asunto(s)
Proteína de la Matriz Oligomérica del Cartílago/sangre , Cartílago Articular/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Envejecimiento/fisiología , Enfermedades Asintomáticas , Biomarcadores/sangre , Fenómenos Biomecánicos/fisiología , Cartílago Articular/fisiopatología , Diagnóstico Precoz , Femenino , Estudios de Seguimiento , Análisis de la Marcha , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico , Osteoartritis de la Rodilla/fisiopatología
12.
Opt Express ; 29(2): 2769-2779, 2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33726467

RESUMEN

Faraday rotation spectroscopy (FRS) employs the Faraday effect to detect Zeeman splitting in the presence of a magnetic field. In this article, we present system design and implementation of radical sensing in a photolysis reactor using FRS. High sensitivity (100 ppb) and time resolved in situ HO2 detection is enabled with a digitally balanced acquisition scheme. Specific advantages of employing FRS for sensing in such dynamic environments are examined and rigorously compared to the more established conventional laser absorption spectroscopy (LAS). Experimental results show that FRS enables HO2 detection when LAS is deficient, and FRS compares favorably in terms of precision when LAS is applicable. The immunity of FRS to spectral interferences such as absorption of hydrocarbons and other diamagnetic species absorption and optical fringing are highlighted in comparison to LAS.

13.
Br J Dermatol ; 185(3): 616-626, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33657677

RESUMEN

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.


Asunto(s)
Síndrome de Stevens-Johnson , Adulto , Niño , Consenso , Humanos , Investigación , Estudios Retrospectivos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/terapia
14.
BMC Neurol ; 21(1): 355, 2021 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-34521381

RESUMEN

BACKGROUND: Continuous spike and wave of sleep with encephalopathy (CSWS) is a rare and severe developmental electroclinical epileptic encephalopathy characterized by seizures, abundant sleep activated interictal epileptiform discharges, and cognitive regression or deceleration of expected cognitive growth. The cause of the cognitive symptoms is unknown, and efforts to link epileptiform activity to cognitive function have been unrevealing. Converging lines of evidence implicate thalamocortical circuits in these disorders. Sleep spindles are generated and propagated by the same thalamocortical circuits that can generate spikes and, in healthy sleep, support memory consolidation. As such, sleep spindle deficits may provide a physiologically relevant mechanistic biomarker for cognitive dysfunction in epileptic encephalopathies. CASE PRESENTATION: We describe the longitudinal course of a child with CSWS with initial cognitive regression followed by dramatic cognitive improvement after treatment. Using validated automated detection algorithms, we analyzed electroencephalograms for epileptiform discharges and sleep spindles alongside contemporaneous neuropsychological evaluations over the course of the patient's disease. We found that sleep spindles increased dramatically with high-dose diazepam treatment, corresponding with marked improvements in cognitive performance. We also found that the sleep spindle rate was anticorrelated to spike rate, consistent with a competitively shared underlying thalamocortical circuitry. CONCLUSIONS: Epileptic encephalopathies are challenging electroclinical syndromes characterized by combined seizures and a deceleration or regression in cognitive skills over childhood. This report identifies thalamocortical circuit dysfunction in a case of epileptic encephalopathy and motivates future investigations of sleep spindles as a biomarker of cognitive function and a potential therapeutic target in this challenging disease.


Asunto(s)
Encefalopatías , Diazepam , Niño , Cognición , Electroencefalografía , Humanos , Sueño
15.
J Appl Microbiol ; 131(3): 1123-1135, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33605066

RESUMEN

AIMS: Vaccines for bovine ephemeral fever virus (BEFV) are available but are difficult to produce, expensive or suffer from genetic instability. Therefore, we designed constructs encoding C-terminally truncated forms (transmembrane anchoring region deleted) of glycoproteins G and GNS such that they were secreted from the cell into the media to achieve high-level antigen expression, correct glycosylation pattern and enable further simple purification with the V5 epitope tag. METHODS AND RESULTS: In this study, synthetic biology was employed to create membrane-bound and secreted forms of G and GNS glycoprotein. Mammalian cell culture was employed as an antigen expression platform, and the secreted forms of G and GNS protein were easily purified from media using a highly effective, single-step method. The V5 epitope tag was genetically fused to the C-termini of the proteins, enabling detection of the antigen through immunoblotting and immunomicroscopy. Our data demonstrated that the C-terminally truncated form of the G glycoprotein was efficiently secreted from cells into the cell media. Moreover the immunogenicity was confirmed in mice test. CONCLUSIONS: The immuno-dot blots showed that the truncated G glycoprotein was present in the total cell extract, and was clearly secreted into the media, consistent with the western blotting data and live-cell images. Our strategy presented the expression of secreted, epitope-tagged, forms of the BEFV glycoproteins such that appropriately glycosylated forms of BEFV G protein was secreted from the BHK-21 cells. This indicates that high-level expression of secreted G glycoprotein is a feasible strategy for large-scale production of vaccines and improving vaccine efficacy. SIGNIFICANCE AND IMPACT OF THE STUDY: The antigen expression strategy designed in this study can produce high-quality recombinant protein and reduce the amount of antigen used in the vaccine.


Asunto(s)
Virus de la Fiebre Efímera Bovina , Fiebre Efímera , Animales , Bovinos , Fiebre Efímera/genética , Fiebre Efímera/prevención & control , Virus de la Fiebre Efímera Bovina/genética , Epítopos/genética , Glicoproteínas/genética , Ratones , Vacunas de Subunidad
16.
J Endocrinol Invest ; 44(12): 2609-2619, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33834419

RESUMEN

PURPOSE: Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD. METHODS: A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m2. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period. RESULTS: Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36-5.60, p = 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03-3.69, p = 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86-10.65, p = 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria. CONCLUSION: Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas , Factores de Crecimiento de Fibroblastos/sangre , Péptido Natriurético Encefálico/sangre , Proteínas de Neoplasias/sangre , Fragmentos de Péptidos/sangre , Proteoglicanos/sangre , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Biomarcadores/sangre , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/etiología , Femenino , Humanos , Pruebas de Función Renal/métodos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos
17.
J Eur Acad Dermatol Venereol ; 35(2): 360-367, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32639047

RESUMEN

Current clinical recommendations suggest that continuous treatment of moderate-to-severe psoriasis with biologic agents is more effective than intermittent treatment in terms of achieving remission and maintaining it. Intermittent treatment, however, may provide an alternative approach in patients unwilling or unable to maintain a continuous regimen, such as those who would prefer a 'treatment vacation' after achieving long-term remission, those who require treatment cessation owing to adverse events, and where insurance arrangements do not provide sufficient cover for continuous treatment. We conducted a literature search of PubMed to identify publications reporting data on the efficacy and safety of intermittent treatment with biologic agents in adults with psoriasis, specifically the use of inhibitors of tumour necrosis factor (adalimumab, certolizumab pegol, etanercept and infliximab), interleukin (IL)-12/IL-23 (ustekinumab), IL-23 (guselkumab) and IL-17 (brodalumab, ixekizumab and secukinumab). From our search, we identified 18 relevant publications reporting the intermittent use of the biologic therapies of interest: five described etanercept, three described adalimumab, two each described infliximab, ixekizumab or ustekinumab, and one each described certolizumab pegol, guselkumab, brodalumab and secukinumab. In general, there were large proportions of patients (≥60%) who were able to re-establish disease control (as defined by each study) following re-treatment, and the safety profiles of the various agents during re-treatment were as anticipated from their profiles observed during continuous dosing. The exception to these general findings was infliximab, which showed the lowest rate of efficacy-endpoint achievement (25% and 38% in two dosing groups evaluated) as well as a higher incidence of adverse infusion reactions compared with continuous dosing. In conclusion, the use of biologic agents in psoriasis is changing and current clinical data suggest that intermittent treatment may provide an effective and well-tolerated option for certain patients.


Asunto(s)
Factores Biológicos , Psoriasis , Adalimumab , Adulto , Anticuerpos Monoclonales/efectos adversos , Factores Biológicos/uso terapéutico , Humanos , Psoriasis/tratamiento farmacológico , Ustekinumab
18.
J Eur Acad Dermatol Venereol ; 35(3): 712-720, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32896010

RESUMEN

BACKGROUND: There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. OBJECTIVE: To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. METHODS: We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. RESULTS: Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. CONCLUSIONS: Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.


Asunto(s)
Síndrome de Stevens-Johnson , Alelos , Anticonvulsivantes , Pueblo Asiatico , Antígenos HLA-B/genética , Hong Kong , Humanos , Taiwán
19.
Zhonghua Yi Xue Za Zhi ; 101(11): 792-797, 2021 Mar 23.
Artículo en Zh | MEDLINE | ID: mdl-33765720

RESUMEN

Objective: To compare the intraoperative blood loss, postoperative drainage and hidden blood loss (HBL) in lumbar posterior lumbar interbody fusion (PLIF) in patients with and without rheumatoid arthritis (RA), and analyze the relevant factors of HBL in RA patients. Methods: Fifty patients with RA (RA group) and 73 patients without RA (NRA group) treated in the Heze Municipal Hospital from January 2014 to April 2019 were enrolled in this study. The basic information, RA information, operation and related blood loss indicators in the two groups were compared. The intraoperative blood loss, postoperative drainage and HBL were the main results. The secondary results were operation time, preoperative and postoperative hematocrit (Hct) and hemoglobin (Hb) and their variation values, cases of anemia before and after surgery, number of new anemia after surgery, autologous blood and allogeneic blood transfusion, etc. The correlation factors of HBL in RA group were analyzed by multi-linear regression model. Results: There were 9 males and 41 females with a mean age of (62±7) years in RA group; and 11 males and 62 females with a mean age of (64±9) years in NRA group. The course of disease in RA group was (14.4±11.2) years, the most common anti-rheumatism drug (DMARDs) were single-drug and combined oral. There was no significant differences between the two groups in the number of vertebral bow screws and intervertebral fusion device. The incidence of surgical complications was comparable between the two groups. Differences between the two groups in total blood loss (TBL), intraoperative blood loss, and postoperative drainage were not statistically significant ((693±315) ml vs (630±365) ml, (454±373) ml vs (414±375) ml and (653±376) ml vs (675±400) ml, t=1.072, 0.388, -0.189, all P>0.05), while the HBL and the percentage of HBL in TBL were lower in the NRA group (t=6.157, 2.965, both P<0.05). According to the layered analysis of the number of surgical segments, the proportion of HBL and the HBL percentage of TBL in the NRA group for the long section (≥3 segments) surgery were better than those in the RA group. The Hct changing value was larger in the RA group than that in the NRA group (P=0.031). However, the difference of Hb reduction between the two groups was not statistically significant (P>0.05). There was no significant difference in anemia and exacerbation of anemia after surgery, allogeneic blood transfusion and the operation duration between the two groups (all P>0.05). A multi-linear regression analysis of HBL showed that higher RA's Steinbrocker grading, did not take DMARDS, Hb changes and infusion of allogeneic blood were independently correlated to HBL (ß=0.363, -0.272, 0.210, 1.204, all P<0.05). Conclusions: There is no difference in TBL, intraoperative blood loss, postoperative drainage and operation duration between the RA and NRA group, while HBL and the proportion of HBL in the TBL are higher in the RA group. The RA group has higher Steinbrocker rating, no DMRDs and more Hb changes.


Asunto(s)
Artritis Reumatoide , Fusión Vertebral , Espondilolistesis , Anciano , Pérdida de Sangre Quirúrgica , Femenino , Humanos , Vértebras Lumbares , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Espondilolistesis/cirugía , Resultado del Tratamiento
20.
Opt Express ; 28(26): 39017-39023, 2020 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-33379459

RESUMEN

In optical spectroscopic systems where unwanted optical scattering cannot be eliminated, Fabry-Pérot etalons cause unpredictable changes in the spectral background. Frequent system calibration is then required to maintain the desired measurement accuracy, which presents a major limitation to the spectrometer. We introduce a computational approach to mitigate the adverse effects of optical fringing without hardware modifications. Motivated by experimental observations of complicated fringe behaviors, we simplify the problem by decomposing the fringe background into component etalons that can be addressed according to their individual characteristics. The effectiveness of the proposed method is demonstrated on a silicon photonic methane sensor, where accurate measurements of methane concentration are obtained from spectral data strongly affected by optical fringes.

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