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1.
Proc Natl Acad Sci U S A ; 121(19): e2307156121, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38683996

RESUMEN

Tourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders progress in the field. We used CRISPR/Cas9 genome editing to generate mice with mutations orthologous to human de novo variants in two high-confidence Tourette genes, CELSR3 and WWC1. Mice with human mutations in Celsr3 and Wwc1 exhibit cognitive and/or sensorimotor behavioral phenotypes consistent with TD. Sensorimotor gating deficits, as measured by acoustic prepulse inhibition, occur in both male and female Celsr3 TD models. Wwc1 mice show reduced prepulse inhibition only in females. Repetitive motor behaviors, common to Celsr3 mice and more pronounced in females, include vertical rearing and grooming. Sensorimotor gating deficits and rearing are attenuated by aripiprazole, a partial agonist at dopamine type II receptors. Unsupervised machine learning reveals numerous changes to spontaneous motor behavior and less predictable patterns of movement. Continuous fixed-ratio reinforcement shows that Celsr3 TD mice have enhanced motor responding and reward learning. Electrically evoked striatal dopamine release, tested in one model, is greater. Brain development is otherwise grossly normal without signs of striatal interneuron loss. Altogether, mice expressing human mutations in high-confidence TD genes exhibit face and predictive validity. Reduced prepulse inhibition and repetitive motor behaviors are core behavioral phenotypes and are responsive to aripiprazole. Enhanced reward learning and motor responding occur alongside greater evoked dopamine release. Phenotypes can also vary by sex and show stronger affection in females, an unexpected finding considering males are more frequently affected in TD.


Asunto(s)
Dopamina , Mutación , Síndrome de Tourette , Animales , Síndrome de Tourette/genética , Síndrome de Tourette/fisiopatología , Síndrome de Tourette/metabolismo , Ratones , Femenino , Masculino , Humanos , Dopamina/metabolismo , Recompensa , Cuerpo Estriado/metabolismo , Modelos Animales de Enfermedad , Aprendizaje/fisiología , Conducta Animal , Inhibición Prepulso/genética , Filtrado Sensorial/genética
2.
Environ Res ; 249: 118320, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38331148

RESUMEN

In a global context, trace element pollution assessment in complex multi-aquifer groundwater systems is important, considering the growing concerns about water resource quality and sustainability worldwide. This research addresses multiple objectives by integrating spatial, chemometric, and indexical study approaches, for assessing trace element pollution in the multi-aquifer groundwater system of the Al-Hassa Oasis, Saudi Arabia. Groundwater sampling and analysis followed standard methods. For this purpose, the research employed internationally recognized protocols for groundwater sampling and analysis, including standardized techniques outlined by regulatory bodies such as the United States Environmental Protection Agency (USEPA) and the World Health Organization (WHO). Average values revealed that Cr (0.041) and Fe (2.312) concentrations surpassed the recommended limits for drinking water quality, posing serious threats to groundwater usability by humans. The trace elemental concentrations were ranked as: Li < Mn < Co < As < Mo < Zn < Al < Ba < Se < V < Ni < Cr < Cu < B < Fe < Sr. Various metal(loid) pollution indices, including degree of contamination, heavy metal evaluation index, heavy metal pollution index, and modified heavy metal index, indicated low levels of groundwater pollution. Similarly, low values of water pollution index and weighted arithmetic water quality index were observed for all groundwater points, signifying excellent groundwater quality for drinking and domestic purposes. Spatial distribution analysis showed diverse groundwater quality across the study area, with the eastern and western parts displaying a less desirable quality, while the northern has the best, making water users in the former more vulnerable to potential pollution effects. Thus, the zonation maps hinted the necessity for groundwater quality enhancement from the western to the northern parts. Chemometric analysis identified both human activities and geogenic factors as contributors to groundwater pollution, with human activities found to have more significant impacts. This research provides the scientific basis and insights for protecting the groundwater system and ensuring efficient water management.


Asunto(s)
Monitoreo del Ambiente , Agua Subterránea , Oligoelementos , Contaminantes Químicos del Agua , Agua Subterránea/análisis , Agua Subterránea/química , Arabia Saudita , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente/métodos , Oligoelementos/análisis
3.
Doc Ophthalmol ; 148(1): 3-14, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38238632

RESUMEN

The full-field stimulus test (FST) is a psychophysical technique designed for the measurement of visual function in low vision. The method involves the use of a ganzfeld stimulator, as used in routine full-field electroretinography, to deliver full-field flashes of light. This guideline was developed jointly by the International Society for Clinical Electrophysiology of Vision (ISCEV) and Imaging and Perimetry Society (IPS) in order to provide technical information, promote consistency of testing and reporting, and encourage convergence of methods for FST. It is intended to aid practitioners and guide the formulation of FST protocols, with a view to future standardisation.


Asunto(s)
Electrorretinografía , Pruebas del Campo Visual , Electrorretinografía/métodos , Sociedades Médicas , Estimulación Luminosa/métodos , Visión Ocular
4.
N Z Vet J ; : 1-12, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38946044

RESUMEN

AIMS: To compare the recovery of lambs, goats, and calves from head-only (HO) or high-frequency head-to-body stunning and evaluate the complementary use of behaviour and electroencephalography (EEG) to assess return to consciousness after electrical stunning in these species. METHODS: Six-month-old lambs, adult goats and calves (< 7 days old) were subjected to reversible head-only stunning (50 Hz, 1 A, 2 seconds) or reversible high-frequency head-to-body stunning (RHTB: HO followed by 2,000 Hz, 2 A, 4-second stun to body). Following stunning, behavioural recovery was assessed in 21 lambs, 22 goats, and 20 calves. Latencies to first perform behaviours (end of convulsions, head lift, attempt to right, successful righting, attempt to stand, successful standing) after stunning were scored from video recordings. Recovery of electrical brain activity indicative of consciousness was assessed using EEG in a separate cohort of minimally-anaesthetised lambs, goats and calves (n = 20 per species). EEG traces collected before and after stunning were classified as normal, epileptiform, isoelectric, or transitional activity. Following stunning, the duration of epileptiform and isoelectric activity combined (states of brain activity incompatible with conscious awareness) was calculated, as was latency to return of normal (pre-stun) EEG. RESULTS: The RHTB stun was reversible in all three species, although one sheep failed to recover and was euthanised. Both methods caused tonic and clonic convulsions in all species. Behavioural recovery of sheep and calves was similar for both methods while goats took longer to recover from RHTB than HO stunning. There was no evidence of differences between methods in the duration of EEG incompatible with consciousness or the latency to recovery of normal EEG. CONCLUSIONS: Head-to-body stunning as applied here produced a reversible electrical stun in lambs, adult goats and young calves, although the benefits in terms of meat quality and operator safety are uncertain. Goats took longer to recover behaviourally from head-to-body stunning, possibly due to disrupted motor function, but there was no indication that post-stun unconsciousness lasted longer than following head-only stunning in any species. The normal behaviour for the animals' developmental age should be considered when deciding on behavioural indicators of recovery. The minimal anaesthesia model provided excellent quality EEG data that was valuable for interpretation of the behavioural responses. CLINICAL RELEVANCE: For the purposes of pre-slaughter stunning of sheep, goats and young calves, recovery appears comparable between the two methods, with all but 1/63 animals in the behaviour study recovering normal function.

5.
Biochemistry ; 62(19): 2816-2827, 2023 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-37699121

RESUMEN

T:G mismatches in mammals arise primarily from the deamination of methylated CpG sites or the incorporation of improper nucleotides. The process by which repair enzymes such as thymine DNA glycosylase (TDG) identify a canonical DNA base in the incorrect pairing context remains a mystery. However, the abundant contacts of the repair enzymes with the DNA backbone suggest a role for protein-phosphate interaction in the recognition and repair processes, where conformational properties may facilitate the proper interactions. We have previously used 31P NMR to investigate the energetics of DNA backbone BI-BII interconversion and the effect of a mismatch or lesion compared to canonical DNA and found stepwise differences in ΔG of 1-2 kcal/mol greater than equivalent steps in unmodified DNA. We have currently compared our results to substrate dependence for TDG, MBD4, M. HhaI, and CEBPß, testing for correlations to sequence and base-pair dependence. We found strong correlations of our DNA phosphate backbone equilibrium (Keq) to different enzyme kinetics or binding parameters of these varied enzymes, suggesting that the backbone equilibrium may play an important role in mismatch recognition and/or conformational rearrangement and energetics during nucleotide flipping or other aspects of enzyme interrogation of the DNA substrate.


Asunto(s)
Nucleótidos , Timina ADN Glicosilasa , Animales , Conformación Molecular , Nucleótidos/metabolismo , ADN/química , Secuencia de Bases , Timina ADN Glicosilasa/química , Reparación del ADN , Mamíferos/metabolismo
6.
Radiology ; 306(1): 279-287, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35972356

RESUMEN

Background The impact of transarterial radioembolization (TARE) of breast cancer liver metastasis (BCLM) on antitumor immunity is unknown, which hinders the optimal selection of candidates for TARE. Purpose To determine whether response to TARE at PET/CT in participants with BCLM is associated with specific immune markers (cytokines and immune cell populations). Materials and Methods This prospective pilot study enrolled 23 women with BCLM who planned to undergo TARE (June 2018 to February 2020). Peripheral blood and liver tumor biopsies were collected at baseline and 1-2 months after TARE. Monocyte, myeloid-derived suppressor cell (MDSC), interleukin (IL), and tumor-infiltrating lymphocyte (TIL) levels were assessed with use of gene expression studies and flow cytometry, and immune checkpoint and cell surface marker levels with immunohistochemistry. Modified PET Response Criteria in Solid Tumors was used to determine complete response (CR) in treated tissue. After log-transformation, immune marker levels before and after TARE were compared using paired t tests. Association with CR was assessed with Wilcoxon rank-sum or unpaired t tests. Results Twenty women were included. After TARE, peripheral IL-6 (geometric mean, 1.0 vs 1.6 pg/mL; P = .02), IL-10 (0.2 vs 0.4 pg/mL; P = .001), and IL-15 (1.9 vs 2.4 pg/mL; P = .01) increased. In biopsy tissue, lymphocyte activation gene 3-positive CD4+ TILs (15% vs 31%; P < .001) increased. Eight of 20 participants (40% [exact 95% CI: 19, 64]) achieved CR. Participants with CR had lower baseline peripheral monocytes (10% vs 29%; P < .001) and MDSCs (1% vs 5%; P < .001) and higher programmed cell death protein (PD) 1-positive CD4+ TILs (59% vs 26%; P = .006) at flow cytometry and higher PD-1+ staining in tumor (2% vs 1%; P = .046). Conclusion Complete response to transarterial radioembolization was associated with lower baseline cytokine, monocyte, and myeloid-derived suppressor cell levels and higher programmed cell death protein 1-positive tumor-infiltrating lymphocyte levels. © RSNA, 2022 Online supplemental material is available for this article.


Asunto(s)
Neoplasias de la Mama , Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Femenino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Mama/terapia , Proyectos Piloto , Neoplasias Hepáticas/patología , Embolización Terapéutica/métodos , Biomarcadores , Carcinoma Hepatocelular/patología , Estudios Retrospectivos , Melanoma Cutáneo Maligno
7.
Osteoarthritis Cartilage ; 31(6): 766-774, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36696941

RESUMEN

OBJECTIVE: To determine the effects of acute (≤7 days) femoral head ischemia on the proximal femoral growth plate and metaphysis in a piglet model of Legg-Calvé-Perthes disease (LCPD). We hypothesized that qualitative and quantitative histological assessment would identify effects of ischemia on endochondral ossification. DESIGN: Unilateral femoral head ischemia was surgically induced in piglets, and femurs were collected for histological assessment at 2 (n = 7) or 7 (n = 5) days post-ischemia. Samples were assessed qualitatively, and histomorphometry of the growth plate zones and primary spongiosa was performed. In a subset of samples at 7 days, hypertrophic chondrocytes were quantitatively assessed and immunohistochemistry for TGFß1 and Indian hedgehog was performed. RESULTS: By 2 days post-ischemia, there was significant thinning of the proliferative and hypertrophic zones, by 63 µm (95% CI -103, -22) and -19 µm (95% CI -33, -5), respectively. This thinning persisted at 7 days post-ischemia. Likewise, at 7 days post-ischemia, the primary spongiosa was thinned to absent by an average of 311 µm (95% CI -542, -82) in all ischemic samples. TGFß1 expression was increased in the hypertrophic zone at 7 days post-ischemia. CONCLUSIONS: Alterations to the growth plate zones and metaphysis occurred by 2 days post-ischemia and persisted at 7 days post-ischemia. Our findings suggest that endochondral ossification may be disrupted at an earlier time point than previously reported and that growth disruption may occur in the piglet model as occurs in some children with LCPD.


Asunto(s)
Enfermedad de Legg-Calve-Perthes , Animales , Porcinos , Enfermedad de Legg-Calve-Perthes/patología , Cabeza Femoral/patología , Placa de Crecimiento/patología , Proteínas Hedgehog , Isquemia
8.
Environ Monit Assess ; 195(8): 999, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37495749

RESUMEN

Water is one of the most abundant resources on earth not evenly distributed. Due to the high shortage of water sources in Igbo-Etiti and intensive agricultural practices in the area, assessment of groundwater pollution and its potential risk to contamination is imperative, as its remediation when contaminated is extremely challenging. Vertical electrical sounding (VES) and physicochemical analysis were carried out in twenty (20) locations and five groundwater samples, respectively, with the aim to evaluate the groundwater pollution indices and the ecological and human health risk associated with its pollution. The VES results delineated five geologic layers and ten characteristic curve types. The fourth layer with the aid of the VES results constrained by the borehole lithologic information on the water bearing geologic unit was delineated as the major exploitable aquifer layer. Results of groundwater vulnerability to pollution classified the area into low (15%), moderate (60%), and high (20%) vulnerability. Physicochemical analysis results on the studied groundwater revealed acidic (pH 4.6) to alkaline (pH 7.2) groundwater conditions. Pollution index of groundwater results delineated a moderate to very high pollution index, with cadmium and arsenic consistently identified as the heavy metals contaminating the groundwater. Ecological risk assessment revealed a moderate to very high integrated potential ecological risk, while human health risk results delineated a target hazard index greater than one in all the studied groundwater samples. This study will serve as a guide to the residents and society in sustainable development decision-making that will preserve the quality of the study area groundwater.


Asunto(s)
Agua Subterránea , Contaminantes Químicos del Agua , Humanos , Monitoreo del Ambiente/métodos , Nigeria , Medición de Riesgo , Agua/análisis , Contaminantes Químicos del Agua/análisis
9.
Biophys J ; 121(9): 1691-1703, 2022 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-35367235

RESUMEN

T:G mismatches in DNA result in humans primarily from deamination of methylated CpG sites. They are repaired by redundant systems, such as thymine DNA glycosylase (TDG) and methyl-binding domain enzyme (MBD4), and maintenance of these sites has been implicated in epigenetic processes. The process by which these enzymes identify a canonical DNA base in the incorrect basepairing context remains a mystery. However, the conserved contacts of the repair enzymes with the DNA backbone suggests a role for protein-phosphate interaction in the recognition and repair processes. We have used 31P NMR to investigate the energetics of DNA backbone BI-BII interconversion, and for this work have focused on alterations to the activation barriers to interconversion and the effect of a mismatch compared with canonical DNA. We have found that alterations to the ΔG of interconversion for T:G basepairs are remarkably similar to U:G basepairs in the form of stepwise differences in ΔG of 1-2 kcal/mol greater than equivalent steps in unmodified DNA, suggesting a universality of this result for TDG substrates. Likewise, we see perturbations to the free energy (∼1 kcal/mol) and enthalpy (2-5 kcal/mol) of activation for the BI-BII interconversion localized to the phosphates flanking the mismatch. Overall our results strongly suggest that the perturbed backbone energetics in T:G basepairs play a significant role in the recognition process of DNA repair enzymes.


Asunto(s)
Timina ADN Glicosilasa , ADN/química , Reparación del ADN , Epigénesis Genética , Humanos , Cinética , Termodinámica , Timina ADN Glicosilasa/química , Timina ADN Glicosilasa/genética , Timina ADN Glicosilasa/metabolismo
10.
Osteoarthritis Cartilage ; 30(9): 1244-1253, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35644462

RESUMEN

OBJECTIVE: To determine if the quantitative MRI techniques T2 and T1ρ mapping are sensitive to ischemic injury to epiphyseal cartilage in vivo in a piglet model of Legg-Calvé-Perthes disease using a clinical 3T MRI scanner. We hypothesized that T2 and T1ρ relaxation times would be increased in the epiphyseal cartilage of operated vs contralateral-control femoral heads 1 week following onset of ischemia. DESIGN: Unilateral femoral head ischemia was surgically induced in eight piglets. Piglets were imaged 1 week post-operatively in vivo at 3T MRI using a magnetization-prepared 3D fast spin echo sequence for T2 and T1ρ mapping and a 3D gradient echo sequence for cartilage segmentation. Ischemia was confirmed in all piglets using gadolinium contrast-enhanced MRI. Median T2 and T1ρ relaxation times were measured in the epiphyseal cartilage of the ischemic and control femoral heads and compared using paired t-tests. Histological assessment was performed on a subset of five piglets. RESULTS: T2 and T1ρ relaxation times were significantly increased in the epiphyseal cartilage of the operated vs control femoral heads (ΔT2 = 11.9 ± 3.7 ms, 95% CI = [8.8, 15.0] ms, P < 0.0001; ΔT1ρ = 12.8 ± 4.1 ms, 95% CI = [9.4, 16.2] ms, P < 0.0001). Histological assessment identified chondronecrosis in the hypertrophic and deep proliferative zones within ischemic epiphyseal cartilage. CONCLUSIONS: T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in vivo at clinical 3T MRI. These techniques may be clinically useful to assess injury and repair to the epiphyseal cartilage to better stage the extent of ischemic damage in Legg-Calvé-Perthes disease.


Asunto(s)
Cartílago Articular , Enfermedad de Legg-Calve-Perthes , Animales , Cartílago/patología , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/patología , Placa de Crecimiento/diagnóstico por imagen , Placa de Crecimiento/patología , Isquemia/diagnóstico por imagen , Isquemia/etiología , Enfermedad de Legg-Calve-Perthes/diagnóstico por imagen , Enfermedad de Legg-Calve-Perthes/patología , Imagen por Resonancia Magnética/métodos , Porcinos
11.
Phys Rev Lett ; 129(24): 244802, 2022 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-36563244

RESUMEN

Creating, manipulating, and detecting coherent electrons is at the heart of future quantum microscopy and spectroscopy technologies. Leveraging and specifically altering the quantum features of an electron beam source at low temperatures can enhance its emission properties. Here, we describe electron field emission from a monocrystalline, superconducting niobium nanotip at a temperature of 5.9 K. The emitted electron energy spectrum reveals an ultranarrow distribution down to 16 meV due to tunable resonant tunneling field emission via localized band states at a nanoprotrusion's apex and a cutoff at the sharp low-temperature Fermi edge. This is an order of magnitude lower than for conventional field emission electron sources. The self-focusing geometry of the tip leads to emission in an angle of 3.7°, a reduced brightness of 3.8×10^{8} A/(m^{2} sr V), and a stability of hours at 4.1 nA beam current and 69 meV energy width. This source will decrease the impact of lens aberration and enable new modes in low-energy electron microscopy, electron energy loss spectroscopy, and high-resolution vibrational spectroscopy.

12.
Curr HIV/AIDS Rep ; 19(2): 154-165, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35147855

RESUMEN

PURPOSE OF REVIEW: Effective ways to diagnose the remaining people living with HIV who do not know their status are a global priority. We reviewed the use of risk-based tools, a set of criteria to identify individuals who would not otherwise be tested (screen in) or excluded people from testing (screen out). RECENT FINDINGS: Recent studies suggest that there may be value in risk-based tools to improve testing efficiency (i.e. identifying those who need to be tested). However, there has not been any systematic reviews to synthesize these studies. We identified 18,238 citations, and 71 were included. The risk-based tools identified were most commonly from high-income (51%) and low HIV (<5%) prevalence countries (73%). The majority were for "screening in" (70%), with the highest performance tools related to identifying MSM with acute HIV. Screening in tools may be helpful in settings where it is not feasible or recommended to offer testing routinely. Caution is needed for screening out tools, where there is a trade-off between reducing costs of testing with missing cases of people living with HIV.


Asunto(s)
Infecciones por VIH , Atención a la Salud , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Prueba de VIH , Humanos , Tamizaje Masivo , Prevalencia
13.
Radiographics ; 42(7): 2014-2036, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36206184

RESUMEN

The motor function of the gastrointestinal tract relies on the enteric nervous system, which includes neurons spanning from the esophagus to the internal anal sphincter. Disorders of gastrointestinal motility arise as a result of disease within the affected portion of the enteric nervous system and may be caused by a wide array of underlying diseases. The etiology of motility disorders may be primary or due to secondary causes related to infection or inflammation, congenital abnormalities, metabolic disturbances, systemic illness, or medication-related side effects. The symptoms of gastrointestinal dysmotility tend to be nonspecific and may cause diagnostic difficulty. Therefore, evaluation of motility disorders requires a combination of clinical, radiologic, and endoscopic or manometric testing. Radiologic studies including fluoroscopy, CT, MRI, and nuclear scintigraphy allow exclusion of alternative pathologic conditions and serve as adjuncts to endoscopy and manometry to determine the appropriate diagnosis. Additionally, radiologist understanding of clinical evaluation of motility disorders is necessary for guiding referring clinicians and appropriately imaging patients. New developments and advances in imaging techniques have allowed improved assessment and diagnosis of motility disorders, which will continue to improve patient treatment options. Online supplemental material is available for this article. ©RSNA, 2022.


Asunto(s)
Enfermedades Gastrointestinales , Motilidad Gastrointestinal , Humanos , Manometría/métodos , Motilidad Gastrointestinal/fisiología , Esófago , Diagnóstico por Imagen
14.
J Reconstr Microsurg ; 38(6): 472-480, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34583393

RESUMEN

BACKGROUND: The lymphaticovenular anastomosis (LVA) has three components, lymphatics, venules, and anastomosis, and all of them influence the anastomotic pressure gradient. Although it has been demonstrated that venule flow dynamics has an independent impact on the outcomes regardless the degeneration status of lymphatic vessels, recipient venules (RV) have been mainly neglected in literature. METHODS: From January 2016 to February 2020, 232 nonconsecutive patients affected by extremity lymphedema underwent LVA, for a total of 1,000 LVAs. Only patients with normal-to-ectasic lymphatic collectors were included to focus the evaluation on the RV only. The preoperative collected data included the location, diameter, and continence of the selected venules, the expected number, the anastomoses configuration, and their flow dynamics according to BSO classification. RESULTS: The 232 patients included 117 upper limb lymphedema (ULL) and 115 lower limb lymphedema (LLL). The average size of RV was 0.81 ± 0.32 mm in end-to-end (E-E), 114 ± 0.17 mm in end-to-side (E-S), 0.39 ± 0.22 mm in side-to-end (S-E), and 0.76 ± 0.38 mm in side-to-side (S-S) anastomoses. According to the BSO classification, on a total of 732 RV, 105(14%) were backflow venules, 136 (19%) were slack, and 491 (67%) were outlet venules. Also, 824 (82%) were E-E, 107 (11%) were E-S, 51 (5%) were S-E, and 18 (2%) were S-S anastomoses. CONCLUSION: Based on 1,000 LVAs with similar lymphatic characteristics, we propose our algorithm that may aid the lymphatic microsurgeon in the selection of RV and the consequent anastomosis configuration, in order of obtain the best flow dynamic through the LVA. This therapeutic study reflects level of evidence IV.


Asunto(s)
Vasos Linfáticos , Linfedema , Algoritmos , Anastomosis Quirúrgica , Humanos , Extremidad Inferior/cirugía , Vasos Linfáticos/cirugía , Linfedema/cirugía , Microcirugia , Extremidad Superior/cirugía , Vénulas/cirugía
15.
Br J Dermatol ; 184(3): 482-494, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32348549

RESUMEN

BACKGROUND: The epidermal barrier is important for water conservation, failure of which is evident in dry-skin conditions. Barrier function is fulfilled by the stratum corneum, tight junctions (TJs, which control extracellular water) and keratinocyte mechanisms, such as organic osmolyte transport, which regulate intracellular water homeostasis. Organic osmolyte transport by keratinocytes is largely unexplored and nothing is known regarding how cellular and extracellular mechanisms of water conservation may interact. OBJECTIVES: We aimed to characterize osmolyte transporters in skin and keratinocytes, and, using transporter inhibitors, to investigate whether osmolytes can modify TJs. Such modification would suggest a possible link between intracellular and extracellular mechanisms of water regulation in skin. METHODS: Immunostaining and quantitative polymerase chain reaction of organic osmolyte-treated organ-cultured skin were used to identify changes to organic osmolyte transporters, and TJ protein and gene expression. TJ functional assays were performed on organic osmolyte-treated primary human keratinocytes in culture. RESULTS: Immunostaining demonstrated the expression of transporters for betaine, taurine and myo-inositol in transporter-specific patterns. Treatment of human skin with either betaine or taurine increased the expression of claudin-1, claudin-4 and occludin. Osmolyte transporter inhibition abolished this response. Betaine and taurine increased TJ function in primary human keratinocytes in vitro. CONCLUSIONS: Treatment of skin with organic osmolytes modulates TJ structure and function, which could contribute to the epidermal barrier. This emphasizes a role for organic osmolytes beyond the maintenance of intracellular osmolarity. This could be harnessed to enhance topical therapies for diseases characterized by skin barrier dysfunction.


Asunto(s)
Queratinocitos , Proteínas de Uniones Estrechas , Epidermis , Humanos , Proteínas de Transporte de Membrana , Piel , Uniones Estrechas
16.
J Public Health (Oxf) ; 43(1): 172-177, 2021 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-31365091

RESUMEN

BACKGROUND: The population of older people in residential homes is projected to rise. There are unrecognized hearing difficulties among residents and prevalence of hearing loss in this population is underreported. This can result in an overestimation of levels of cognitive impairment. Untreated hearing loss is associated with social isolation, depression, disruptive behaviour and cognitive decline. This study aimed to explore the provision of hearing care (hearing assessment, rehabilitation and staff training) in Scottish care homes for older people. METHODS: A survey comprising 18 questions was distributed to the managers (or designated staff members) of 659 care homes across Scotland. RESULTS: Responses were obtained from 154 care homes. The results support existing evidence that hearing is not assessed in the majority of homes, resulting in under detection of hearing loss. Staff lack training in supporting residents' hearing needs. Access to hearing care in residential homes differs across health board areas. CONCLUSIONS: There is an urgent requirement for hearing assessment of older adults on admission to residential care. Care providers require this information to construct effective care plans and mitigate the effects of hearing loss. Those responsible for providing hearing rehabilitation services require information about service users to address any unmet need.


Asunto(s)
Hogares para Ancianos , Casas de Salud , Anciano , Atención a la Salud , Audición , Humanos , Escocia/epidemiología
17.
Health Educ Res ; 36(1): 126-139, 2021 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-33367691

RESUMEN

teen Mental Health First Aid (teenMHFA) is a school-based mental health program that trains adolescents to support peers who are experiencing mental health problems or crises. The program has been evaluated for adolescents aged 15-18 years as part of a randomized controlled trial, however qualitative feedback from students on their perceptions of the program is yet to be explored. The current study describes the perspectives of students who took part in the trial. Feedback on the perceived strengths and weaknesses of the program was provided by 979 Year 10 students (M = 15.82 years, female = 43.94%, English as a first language = 72.77%) at four government funded public schools in Melbourne, Australia via online surveys. A content and thematic analysis was performed on the data using a six-step process. Students generally found the program relevant and they connected with the visual material, personal stories and interactive activities. Suggestions for improvements included encouraging active student participation in classroom discussion and providing opportunities to practice skills. School-based mental health education can benefit from input from stakeholder perspectives, particularly when designing mental health content for delivery by external trainers.


Asunto(s)
Educación en Salud , Instituciones Académicas , Adolescente , Australia , Femenino , Humanos , Grupo Paritario , Evaluación de Programas y Proyectos de Salud , Estudiantes
18.
Radiology ; 297(2): 374-379, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32808887

RESUMEN

Background There is increasing research attention on the impact of overnight work on radiologist performance. Prior studies on overnight imaging interpretive errors have focused on radiology residents, not on the relative performance of board-eligible or board-certified radiologists at night compared with during the day. Purpose To analyze the rate of clinically important interpretation errors on CT examinations of the abdomen, pelvis, or both ("body CT studies") committed by radiology fellows working off-hours based on day or night assignment. Materials and Methods Between July 2014 and June 2018, attending physicians at one tertiary care institution reviewed all body CT studies independently interpreted off-hours by radiologists in an academic fellowship within 10 hours of initial interpretation. Discrepancies affecting acute or follow-up clinical care were classified as errors. In this retrospective study, the error rate for studies interpreted during the day (between 7:00 am and 5:59 pm) was compared with that of studies interpreted at night (between 6:00 pm and 6:59 am). Error rate in the first half of day and night assignments was compared with error rate in the latter half. Statistical analyses used χ2 tests and general estimating equations; significance was defined as P < .05. Results There were 10 090 body CT studies interpreted by 32 radiologists. Forty-four of 2195 daytime studies (2.0%) had errors compared with 240 of 7895 nighttime studies (3.0%; P = .02). Twenty-two of 32 (69%) radiologists had higher error rates for night cases (P = .03). There were more errors in the last half of a night assignment (125 of 3358, 3.7%; P = .002) compared with the first half (115 of 4537, 2.5%). Conclusion On the basis of a subspecialty review, clinically important off-hours body CT interpretation errors occurred more frequently overnight and more frequently in the latter half of assignments, with more radiologists having worse error rates at night compared with the day. © RSNA, 2020 See also the editorial by Bruno in this issue.


Asunto(s)
Atención Posterior , Competencia Clínica , Errores Diagnósticos/estadística & datos numéricos , Internado y Residencia , Cuerpo Médico de Hospitales , Radiología/educación , Tomografía Computarizada por Rayos X , Anciano , Certificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
19.
Osteoarthritis Cartilage ; 28(9): 1235-1244, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32278071

RESUMEN

OBJECTIVE: Evaluate articular cartilage by magnetic resonance imaging (MRI) T2∗ mapping within the distal femur and proximal tibia in adolescents with juvenile osteochondritis dissecans (JOCD). DESIGN: JOCD imaging studies acquired between August 2011 and February 2019 with clinical and T2∗ mapping MRI knee images were retrospectively collected and analyzed for 31 participants (9F/22M, 15.0 ± 3.8 years old) with JOCD lesions in the medial femoral condyle (MFC). In total, N = 32 knees with JOCD lesions and N = 14 control knees were assessed. Mean T2∗ values in four articular cartilage regions-of-interest (MFC, lateral femoral condyle (LFC), medial tibia (MT), and lateral tibia (LT)) and lesion volume were measured and analyzed using Wilcoxon-rank-sum tests and Spearman correlation coefficients (R). RESULTS: Mean ± standard error T2∗ differences observed between the lesion-sided MFC and the LFC in JOCD-affected knees (28.5 ± 0.9 95% confidence interval [26.8, 30.3] vs 26.3 ± 0.7 [24.8, 27.7] ms, P = 0.088) and between the affected- and control-knee MFC (28.5 ± 0.9 [26.8, 30.3] vs 28.5 ± 0.6 [27.1, 29.9] ms, P = 0.719) were nonsignificant. T2∗ was significantly increased in the lesion-sided MT vs the LT for the JOCD-affected knees (21.5 ± 0.7 [20.1, 22.9] vs 18.0 ± 0.7 [16.5, 19.5] ms, P = 0.002), but this same difference was also observed between the MT and LT in control knees (21.0 ± 0.6 [19.7, 22.3] vs 18.1 ± 1.1 [15.8, 20.4] ms, P = 0.037). There was no significant T2∗ difference between the affected- and control-knee MT (21.5 ± 0.7 [20.1, 22.9] vs 21.0 ± 0.6 [19.7, 22.3] ms, P = 0.905). T2∗ within the lesion-sided MFC was not correlated with patient age (R = 0.20, P = 0.28) or lesion volume (R = 0.06, P = 0.75). T2∗ values were slightly increased near lesions in later-stage JOCD subjects but without statistical significance. CONCLUSIONS: T2∗ relaxations times were not significantly different from control sites in the articular cartilage overlying JOCD lesions in the MFC or adjacent MT cartilage in early-stage JOCD.


Asunto(s)
Cartílago Articular/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Osteocondritis Disecante/diagnóstico por imagen , Adolescente , Edad de Inicio , Niño , Femenino , Fémur/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Tibia/diagnóstico por imagen , Adulto Joven
20.
J Microsc ; 277(3): 140-153, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31070241

RESUMEN

A time-lapse study of thermomechanical fatigue damage has been undertaken using three-dimensional X-ray computer tomography. Morphologies were extracted from tomography data and integrated with data from microscopy modalities at different resolution levels. This enables contextualization of some of the fine-scale properties which underpin the large-scale damage observed via tomography. Lateral views of crack development are presented, which show networks analogous to mud-cracks. Crack fronts which develop in the most porous regions within the sintered attachment layer travel across the boundary into the copper substrate. The propagation characteristics of these cracks within the substrate are analysed. Evidence is provided of heterogeneous densification within the sintered joint under power cycling, and this is shown to play a major role in driving the initiation and propagation of the cracks. Examination of the texture (differing levels of X-ray absorption) of virtual cross-sectional images reveals the origins of the nonuniformity of densification. Finally, cracks within the sintered joint are shown to have a negligible impact on the conduction pathway of the joint due to their aspect ratio and orientation with respect to the assembly. LAY DESCRIPTION: This paper concerns the use of three-dimensional (3D) X-ray tomography, a nondestructive technique, to perform cradle-to-grave studies of sintered nanosilver die-attachments under operation. Sintered nanosilver die-attachments have been proposed as a more reliable and environmentally friendly alternative to solder alloy joints for emerging power electronics module designs. However, their degradation mechanisms are not as well understood. This same sample-study is about observing how the fine-scale structure of a sintered attachment evolves and degrades over time. Using 3D tomography affords otherwise infeasible perspectives, such as virtual cross-sections in the lateral plane of the attachment. These perspectives provide qualitative information which elucidates the degradation mechanisms. They demonstrate, for example, that the structure of the sintered attachment densifies under operation, and a consequence of this is the formation of shrinkage cracks in the most porous regions, much like mud-cracks. Other imaging techniques (metallographic etching and scanning electron microscopy) have been used in correlation with 3D renderings of these cracks to analyse their propagation and reveal their relationship both with the internal structure of the sintered attachment itself, and the structure of the substrate to which it is joined. It is shown that the cracks develop within the sintered attachment layer and eventually cross over into the substrate. A comparison of two sintered attachments with contrasting bulk porosities allows the effect of initial bond quality on crack development to be examined.

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