RESUMEN
The endoplasmic reticulum (ER) is a versatile organelle with diverse functions. Through superresolution microscopy, we show that the peripheral ER in the mammalian cell adopts two distinct forms of tubules. Whereas an ultrathin form, R1, is consistently covered by ER-membrane curvature-promoting proteins, for example, Rtn4 in the native cell, in the second form, R2, Rtn4 and analogs are arranged into two parallel lines at a conserved separation of â¼105 nm over long ranges. The two tubule forms together account for â¼90% of the total tubule length in the cell, with either one being dominant in different cell types. The R1R2 dichotomy and the final tubule geometry are both coregulated by Rtn4 (and analogs) and the ER sheetmaintaining protein Climp63, which, respectively, define the edge curvature and lumen height of the R2 tubules to generate a ribbon-like structure of well-defined width. Accordingly, the R2 tubule width correlates positively with the Climp63 intraluminal size. The R1 and R2 tubules undergo active remodeling at the second/subsecond timescales as they differently accommodate proteins, with the former effectively excluding ER-luminal proteins and ER-membrane proteins with large intraluminal domains. We thus uncover a dynamic structural dichotomy for ER tubules with intriguing functional implications.
Asunto(s)
Citoesqueleto , Retículo Endoplásmico , Animales , Citoesqueleto/metabolismo , Retículo Endoplásmico/metabolismo , Mamíferos , MicroscopíaRESUMEN
Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder of DNA repair and transcription with developmental delay and abnormalities in brain, eye, skin, nervous, and musculoskeletal systems. We followed a cohort of 37 patients with TTD at the National Institutes of Health (NIH) from 2001 to 2019 with a median age at last observation of 12 years (range 2-36). Some children with TTD developed rapidly debilitating hip degeneration (DHD): a distinctive pattern of hip pain, inability to walk, and avascular necrosis on imaging. Ten (27%) of the 37 patients had DHD at median age 8 years (range 5-12), followed by onset of imaging findings at median age 9 years (range 5-13). All 10 had mutations in the ERCC2/XPD gene. In 7 of the 10 affected patients, DHD rapidly became bilateral. DHD was associated with coxa valga, central osteosclerosis with peripheral osteopenia of the skeleton, and contractures/tightness of the lower limbs. Except for one patient, surgical interventions were generally not effective at preventing DHD. Four patients with DHD died at a median age of 11 years (range 9-15). TTD patients with ERCC2/XPD gene mutations have a high risk of musculoskeletal abnormalities and DHD leading to poor outcomes. Monitoring by history, physical examination, imaging, and by physical medicine and rehabilitation specialists may be warranted.
Asunto(s)
Enfermedades Óseas Metabólicas , Contractura , Coxa Valga , Osteonecrosis , Osteosclerosis , Síndromes de Tricotiodistrofia , Niño , Humanos , Preescolar , Adolescente , Adulto Joven , Adulto , Síndromes de Tricotiodistrofia/diagnóstico , Síndromes de Tricotiodistrofia/genética , Coxa Valga/complicaciones , Mutación , Contractura/genética , Contractura/complicaciones , Enfermedades Óseas Metabólicas/genética , Proteína de la Xerodermia Pigmentosa del Grupo D/genéticaRESUMEN
We introduce a strategy to optimize the photoswitching behavior of rhodamines for (d)STORM super-resolution microscopy. By replacing the benzene ring in the rhodamine core with a permanently charged 1,3-disubstituted imidazolium, the resultant dyes are markedly sensitized toward photoswitching, and exhibit outstanding (d)STORM performance with fast on-off switching, long-lasting blinking, and bright single-molecule emission. We thus attain excellent (d)STORM images under green excitation that are on par with the "ideal" red-excited dyes, including for difficult structures such as the mammalian actin cytoskeleton, and demonstrate high-quality two-color three-dimensional (d)STORM.
RESUMEN
BACKGROUND: Sutures can tear through tissue, but little data exist on the relative ability of different suture gauges and suture types to cut into the skin. OBJECTIVE: To quantify the relative ability of various sutures to cut into and tear through the skin. METHODS AND MATERIALS: We tested 4 suture types (polypropylene, nylon, polyglactin 910, and poliglecaprone 25) at 2 gauges each (3-0 and 5-0) in their ability to cut into and tear through an artificial skin substitute comprised of a 1-mm thick silicone sheet. The force required to cut into and through the skin substitute was measured using a digital force gauge that generated a force-time curve. The suture diameters were verified using both a precision caliper micrometer and an eyepiece micrometer with the microscope. Statistical analysis was performed using the Student t-test and analysis of variance. RESULTS: All 5-0 suture types required less force to cut into and tear through the skin substitute than their 3-0 counterparts. Among each suture gauge, there was no significant difference in tear-through force regardless of the suture type. CONCLUSION: Compared with larger gauge sutures, smaller gauge sutures more easily cut into and tear through skin substitute.
Asunto(s)
Ensayo de Materiales/métodos , Piel Artificial , Técnicas de Sutura/instrumentación , Suturas , Humanos , Resistencia a la TracciónRESUMEN
ABSTRACT: Radiation can induce changes to skeletal muscle cells that may mimic and thus be confused with cells of atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma, spindle cell squamous cell carcinoma, and other spindle soft-tissue tumors. An 80-year-old White man presented for Mohs micrographic surgery of an AFX on the left lateral neck. The medical history was notable for a tongue squamous cell carcinoma 9 years before that had been treated with wide local excision, left neck dissection, and radiation to the oral cavity and left neck. Frozen sections from the first stage of Mohs did not show typical AFX, but did reveal patchy clusters of atypical spindled and epithelioid cells, some with multiple nuclei. Because of the unusual appearance of these cells, Mohs micrographic surgery was halted, and the frozen tissue block was sent for permanent pathology examination. The cells on permanent sections stained positive for desmin, revealing them to be of skeletal muscle origin (in this case damaged platysma muscle because of late postradiation changes). It is thus important for the Mohs surgeon and the consultant dermatopathologist to be aware of the unusual histologic appearance of irradiated skeletal muscle to avoid confusion with other spindle cell tumors.
Asunto(s)
Histiocitoma Fibroso Maligno/diagnóstico , Cirugía de Mohs , Músculo Esquelético/patología , Traumatismos por Radiación/patología , Neoplasias Cutáneas/diagnóstico , Anciano de 80 o más Años , Diagnóstico Diferencial , Secciones por Congelación , Histiocitoma Fibroso Maligno/patología , Humanos , Masculino , Músculo Esquelético/efectos de la radiación , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/patología , Neoplasias Cutáneas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Neoplasias de la Lengua/radioterapiaRESUMEN
BACKGROUND: Sutures can tear through thin skin, especially in the elderly. To reinforce thin skin, several materials have been suggested through which sutures may be placed. OBJECTIVE: To evaluate the relative tear-through resistance to suture provided by various materials applied to a skin substitute. MATERIALS/METHODS: We measured the force needed for 3-0 polypropylene suture to tear through an artificial skin substitute, both alone and after various materials were applied. These materials included wound closure tapes, nonwoven polyester tape, hydrocolloid dressing, polyethylene film, and cyanoacrylate glue. The Student t-test and one-way analysis of variance were used to determine differences in the mean forces. RESULTS: Reinforced wound closure tape and nonwoven polyester tape were superior to the other materials, and provided a 3.1-fold and 3.6-fold increase in tear-through resistance, respectively, compared with skin substitute alone (p < .001). Orientation of wound closure tape and nonwoven polyester tape with their reinforcing fibers placed parallel to the skin substitute edge provided increased tear-through resistance compared with perpendicular placement. Affixing these latter materials with liquid adhesive also improved holding strength. CONCLUSION: Reinforced wound closure tape and nonwoven polyester tape, when applied to a skin substitute, provide significantly increased tear-through resistance to suture compared with skin substitute alone.
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Procedimientos Quirúrgicos Dermatologicos/instrumentación , Herida Quirúrgica/cirugía , Técnicas de Sutura/instrumentación , Suturas/efectos adversos , Vendajes , Procedimientos Quirúrgicos Dermatologicos/efectos adversos , Humanos , Ensayo de Materiales , Poliésteres/química , Piel Artificial , Técnicas de Sutura/efectos adversos , Adhesivos Tisulares/químicaAsunto(s)
Antebrazo , Tendones , Antebrazo/cirugía , Humanos , Músculo Esquelético , Tendones/cirugíaRESUMEN
The prevalence of low vitamin D levels and associated risks has led to an increase in supplementation. However, a "U-shaped" relationship has been suggested between vitamin D status and adverse effects, with risks observed both in low and high levels. While risks associated with low levels of vitamin D have been extensively studied, the risks of higher levels of vitamin D have not been as widely circulated. We sought to describe key observed adverse risks with vitamin D supplementation and higher serum 25(OH)-D levels in healthy adult populations.
Asunto(s)
Suplementos Dietéticos/efectos adversos , Vitamina D/efectos adversos , Vitamina D/sangre , Vitaminas/efectos adversos , Vitaminas/sangre , Accidentes por Caídas/estadística & datos numéricos , Asma/epidemiología , Enfermedades Cardiovasculares/epidemiología , Fracturas Óseas/epidemiología , Humanos , Hidroxicolecalciferoles/sangre , Mortalidad , Neoplasias/epidemiología , Neoplasias/mortalidad , Guías de Práctica Clínica como Asunto , Prevalencia , Factores de Riesgo , Vitamina D/administración & dosificación , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/prevención & control , Vitaminas/administración & dosificaciónRESUMEN
BACKGROUND: Topical 5% 5-fluorouracil (5-FU) is known to cause toxicity, such as erythema, pain, and crusting/erosions. OBJECTIVES: We sought to develop a scale to measure this toxicity and test the scale for reliability. METHODS: A scale was developed involving four parameters: erythema severity, percentage of face involved in erythema, crusting/erosions severity, and percentage of face involved in crusting/erosions. Thirteen raters graded 99 sets of photographs from the Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial using these parameters. RESULTS: Intraclass correlation overall for 13 raters was 0.82 (95% CI 0.77-0.86). There was no statistically significant trend in reliability by level of training in dermatology. CONCLUSIONS: This scale is a reliable method of evaluating the severity of toxicity from topical 5-fluorouracil and can be used by dermatologists and nondermatologists alike.
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Antimetabolitos Antineoplásicos/efectos adversos , Erupciones por Medicamentos/patología , Eritema/patología , Dermatosis Facial/patología , Fluorouracilo/efectos adversos , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Erupciones por Medicamentos/etiología , Eritema/inducido químicamente , Dermatosis Facial/inducido químicamente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
IMPORTANCE: Cutaneous T-cell lymphoma (CTCL) incidence and survival have been increasing steadily for over 25 years. OBJECTIVE: We sought to measure changes in CTCL incidence trends and survival rates. DESIGN, SETTING, AND PARTICIPANTS: Population-based study. The CTCL incidence and survival data were obtained from the 9 original registries (1973-2009) and the 4 additional registries (1992-2009) of the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute (NCI). Trend analysis was performed using the Joinpoint Regression Program provided by the NCI. Survival analysis was performed using the SeerSTAT statistical software of the NCI. The total number of cases of CTCL from 1973 to 2009 was 6230. MAIN OUTCOMES AND MEASURES: Diagnoses of CTCL. RESULTS: Overall CTCL incidence has stabilized since 1998 (95% CI, 1994-2002), with an annual percent change (APC) of 5.7% from 1973 to 1998 (95% CI, 4.9%-6.5%) and an APC of 0.1% from 1998 to 2009 (95% CI, -1.4% to 1.5%). Similar incidence stabilization patterns were found in subgroup analyses of race, sex, age, diagnosis, and registry. Five-year CTCL survival rates increased until 2004. CONCLUSIONS AND RELEVANCE: The incidence of CTCL is no longer increasing. Causes for this trend change may include real incidence stabilization, stabilization of physician detection, or artifact.
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Linfoma Cutáneo de Células T/epidemiología , Programa de VERF/tendencias , Neoplasias Cutáneas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Linfoma Cutáneo de Células T/diagnóstico , Masculino , Persona de Mediana Edad , Sistema de Registros , Neoplasias Cutáneas/diagnóstico , Tasa de Supervivencia , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Previously considered safe for typical use, concerns have recently been expressed regarding the potential effect of compact fluorescent lamps (CFLs) on human skin and, in particular, on skin cancer risk. OBJECTIVE: We sought to address this concern by reviewing the current literature on CFLs, ultraviolet (UV) radiation, and photocarcinogenic exposure. RESULTS: On average, the UV radiation from CFLs and subsequent carcinogenic exposure is lower than that from incandescent bulbs. However, defective bulbs can emit higher levels of UV radiation, which may cause significant damage. CONCLUSION: Our review calls for further investigation to determine how frequently these bulbs are sufficiently defective to lead to adverse effects.
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Fluorescencia , Artículos Domésticos/instrumentación , Iluminación/instrumentación , Neoplasias Cutáneas/etiología , Rayos Ultravioleta/efectos adversos , HumanosRESUMEN
Invasive squamous cell carcinoma (SCC) of the skin is one of the most common cancers in the United States, with no proven means for prevention other than systemic retinoids, which have significant toxicity, and sunscreen. We sought to determine the risk factors for invasive SCC on the face or ears in a high-risk population comprising 1,131 veterans in the Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) Trial. Participants were required to have been diagnosed with at least two keratinocyte carcinomas (KCs) in the 5 years prior to enrollment. The median duration of follow-up was 3.7 years. Twenty-three percent of the participants developed a new invasive SCC, and the cumulative risk of invasive SCC was 30% at 5 years. The following factors independently predicted for new invasive SCCs: number of invasive SCCs and number of in situ SCCs in the 5 years prior to enrollment, actinic keratoses count at enrollment, a history of ever use of topical 5-fluorouracil, and total occupational time spent outdoors. In contrast, the use of angiotensin-convering enzyme inhibitors or angiotensin receptor blockers during the study and a history of warts anywhere on the body were found to protect against new invasive SCCs. These independent predictors remained the same for all SCCs (invasive and in situ combined). The number of basal cell carcinomas in the 5 years prior to enrollment, sunburns, sun sensitivity, and recreational sun exposure were not associated with new SCCs. These findings identify key risk factors for additional SCCs in patients with multiple prior KCs, and suggest that a history of warts may be associated with reduced SCC risk.
Asunto(s)
Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/prevención & control , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/prevención & control , Tretinoina/uso terapéutico , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Carcinoma Basocelular/epidemiología , Carcinoma Basocelular/prevención & control , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Factores de Riesgo , Quemadura Solar/epidemiología , Protectores Solares/uso terapéutico , Veteranos/estadística & datos numéricos , Verrugas/epidemiologíaRESUMEN
OBJECTIVE: To gain insight into reducing melanoma mortality by examining epidemiologic trends by subtype with emphasis on the contribution of each subtype to melanoma-related death. DESIGN: Retrospective population-based cohort study. SETTING: Original 9 registries of the Surveillance, Epidemiology, and End Results Program from 1978 to 2007. PARTICIPANTS: A total of 111,478 patients with histologically confirmed invasive melanoma. MAIN OUTCOME MEASURE: Proportion of ultimately fatal melanomas by subtype. RESULTS: Among melanomas of known subtype, superficial spreading melanoma comprised 66% of incident melanomas and 46% of ultimately fatal melanomas; nodular melanoma comprised 14% of incident melanomas and 37% of ultimately fatal melanomas. For superficial spreading melanoma, overall incidence per 100,000 per year increased (from 4.28 to 6.63), ultimately fatal incidence remained stable (at 0.56 to 0.51), and 10-year relative survival increased (from 90.6% to 96.5%) when comparing successive 5-year intervals. In contrast, for nodular melanoma, the overall incidence (1.30-1.32), ultimately fatal incidence (0.46-0.44), and 10-year relative survival rate (61.8%-61.5%) remained stable. Epidemiologic trends of melanoma, not otherwise specified, were similar to superficial spreading melanoma. There was a strong negative correlation between the proportion of melanoma, not otherwise specified, among all melanomas, and the proportion of superficial spreading melanoma, among melanomas of known subtype (r = -0.80; P = .01), across the registries. CONCLUSIONS: Superficial spreading and nodular melanoma constitute similar proportions of ultimately fatal melanomas. Although incidence of and survival from superficial spreading melanoma have increased from 1978 to 2007, neither the incidence of nor survival from nodular melanoma has changed. Public health efforts should include a focus on nodular melanoma for maximum reduction of melanoma mortality.
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Melanoma/mortalidad , Melanoma/patología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Estudios de Cohortes , Femenino , Humanos , Masculino , Melanoma/clasificación , Estudios Retrospectivos , Neoplasias Cutáneas/clasificación , Estados Unidos/epidemiologíaRESUMEN
This article examines the overall organization of services and delivery of health care in the United States. Health maintenance organization, fee-for-service, preferred provider organizations, and the Veterans Health Administration are discussed, with a focus on structure, outcomes, and areas for improvement. An overview of wait times, malpractice, telemedicine, and the growing population of physician extenders in dermatology is also provided.