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Urine release (micturition) serves an essential physiological function as well as a critical role in social communication in many animals. Here, we show a combined effect of olfaction and social hierarchy on micturition patterns in adult male mice, confirming the existence of a micturition control center that integrates pro- and anti-micturition cues. Furthermore, we demonstrate that a cluster of neurons expressing corticotropin-releasing hormone (Crh) in the pontine micturition center (PMC) is electrophysiologically distinct from their Crh-negative neighbors and sends glutamatergic projections to the spinal cord. The activity of PMC Crh-expressing neurons correlates with and is sufficient to drive bladder contraction, and when silenced impairs micturition behavior. These neurons receive convergent input from widespread higher brain areas that are capable of carrying diverse pro- and anti-micturition signals, and whose activity modulates hierarchy-dependent micturition. Taken together, our results indicate that PMC Crh-expressing neurons are likely the integration center for context-dependent micturition behavior.
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Hormona Liberadora de Corticotropina/metabolismo , Contracción Muscular/fisiología , Neuronas/fisiología , Puente/fisiología , Vejiga Urinaria/fisiología , Micción/fisiología , Animales , Femenino , Ácido Glutámico/fisiología , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismo , Puente/citología , Olfato , Médula Espinal/citología , Médula Espinal/fisiología , Vejiga Urinaria/inervaciónRESUMEN
The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.
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Carcinoma de Células de Merkel , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapiaRESUMEN
Sexual and gender minority adolescents face specific stressors associated with their minority status, leading to compromised socioemotional outcomes and sleep. Sleep patterns have, in turn, been found to predict socioemotional outcomes. As such, we aimed to investigate whether healthy sleep patterns prospectively predicted socioemotional outcomes, and whether associations varied as a function of sexual and gender minority status. We conducted a secondary data analysis among adolescents at age 14 to 17, from a nationally representative prospective cohort in the United Kingdom (N = 8923, mean age = 13.8), with 7021 cisgender heterosexual, 1801 sexual minority, and 101 gender minority adolescents. Indicators of socioemotional outcomes included self-esteem, emotional well-being, peer relationships, and relationship with parents. The results showed that gender minority adolescents reported the worst sleep patterns and socioemotional outcomes, followed by sexual minority and cisgender heterosexual adolescents. Results from multi-group path analyses showed that emotional well-being, self-esteem, and peer relationships at age 17 were prospectively predicted by sleep patterns and the associations were moderated by sexual and gender minority status. Influence of sleep patterns, particularly sleep initiation problems and frequent awakening, on socioemotional outcomes was greater among gender minority adolescents, when compared to cisgender heterosexual adolescents. In conclusion, positive socioemotional outcomes were predicted by healthy sleep patterns. The potential role of sleep health in optimizing socioemotional outcomes among sexual and gender minority adolescents might warrant further investigation in prevention or intervention studies.
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Conducta Sexual , Minorías Sexuales y de Género , Humanos , Adolescente , Estudios Longitudinales , Estudios Prospectivos , Conducta Sexual/psicología , Sueño , Identidad de GéneroRESUMEN
Sexual minority adolescents (SMA) have a disproportionately high prevalence of victimisation, self-harm, and depressed mood, relative to the general population. Yet, the contributing and mechanistic factors are unclear. We aim to explore the directional relationship between victimisation and self-harm and depressed mood, with poor sleep quality as a possible mediator. A secondary data analysis was conducted using a nationally representative birth cohort in the United Kingdom, where participants self-identified as sexual minority (N = 1922, aged 11-13, 67.1% female) and their parents completed questionnaires and interviews when the participants were aged 11, 14 and 17. Logistic and linear regression were used to test whether victimisation prospectively predicted self-harm and depressed mood with mediation analyses conducted to assess if sleep onset latency and nocturnal awakening mediated their relationships. After adjusting for demographic factors and baseline self-harm and depressed mood, victimisation at age 11 significantly predicted self-harm (OR = 1.40, p < .01) and depressed mood (B = 0.024, SE = 0.01, p < .05) at age 17. In the mediation analyses, frequent nocturnal awakening at age 14, but not sleep onset latency, significantly mediated the effect of victimisation at age 11 on self-harm (indirect effect B = 0.008, SE = 0.004, 95%CI = 0.001-0.017) and depressed mood (indirect effect B = 0.005, SE = 0.002 95%CI = 0.001-0.010) at age 17. Our findings supported that victimisation contributed to negative mental health among SMA. Poor sleep quality could be an indicator of maladjustment with victimisation, which further increased vulnerability to negative mental health. Victimisation and sleep quality could be important assessment targets in mental health campaign among sexual minority adolescents.
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Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.
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Carcinoma Basocelular , Neoplasias Cutáneas , Humanos , Estados Unidos/epidemiología , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/epidemiología , Carcinoma Basocelular/etiología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/etiología , Luz Solar , Oncología Médica , IncidenciaRESUMEN
BACKGROUND: Mycosis fungoides (MF) in children is a rare disease and there are limited data regarding the behavior of the disease in this age group. We aimed to collect additional data to better understand the clinicopathologic features of MF in children. MATERIALS AND METHODS: This study was a retrospective analysis of pediatric MF patients (diagnosed at age 0 to 18 y). RESULTS: Thirteen pediatric patients with MF were identified. Female predominance was observed with a ratio of 1.6:1. Median values for age of onset of skin lesions and age at the time of histologic diagnosis were 5 and 12 years, respectively. All patients had early stage (stage IA to IIA) of MF at the time of diagnosis. Hypopigmented MF comprised 77% of all study patients, followed by classic MF (15%) and pagetoid reticulosis (8%). The lower extremity (especially proximal leg) followed by trunk and upper extremity were most commonly affected sites. Seven of 9 patients who had available immunohistochemistry data showed CD8 + predominance. Five of 8 patients whose follow-up data was available, achieved complete response with narrowband ultraviolet B treatment, while 2 and 1 had near complete response and partial response, respectively. CONCLUSIONS: Our study demonstrated female sex and CD8 + profile predominance. Hypopigmented MF constituted the majority of cases. We observed good responses with narrowband ultraviolet B treatment.
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Micosis Fungoide , Enfermedades de la Piel , Neoplasias Cutáneas , Adolescente , Linfocitos T CD8-positivos/patología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Micosis Fungoide/patología , Estudios Retrospectivos , Neoplasias Cutáneas/patologíaRESUMEN
OBJECTIVE: Accumulating evidence has suggested bidirectionality between sleep problems and depression, but the underlying mechanism is unclear. We assessed the role of sleep in inhibitory control ability with emotional stimuli, which has been shown to be suboptimal among individuals with depression and proposed to perpetuate depressive symptoms. METHODS: Emerging adults (aged 18-25 years, 64.6% female) were screened for depressive and other mental disorders by structured clinical interview and questionnaire. Individuals with depressive disorders were assigned to have a polysomnography-monitored daytime sleep opportunity (Sleep-Dep, n = 20), whereas nondepressed individuals were randomized to either have daytime sleep (Sleep-Ctrl, n = 27) or stay awake (Wake-Ctrl, n = 18). Participants completed the Affective Go/No-Go Task two times, separated by experimental conditions. RESULTS: A factorial model with a between-subject factor (Sleep-Dep/Sleep-Ctrl/Wake-Ctrl) and a within-subject factor (test 1/test 2) was used to assess if the groups differed in inhibitory control across test sessions, as inferred by changes in d-prime and false alarm rates (FA). Results from mixed factorial models showed a significant interaction effect between time and group on FA in the block with neutral faces as the target and happy faces as the nontarget (F(2,61) = 5.15, pfdr = .045). Although Sleep-Dep had decreased FA after sleep (t(19) = 2.94, pfdr = .050), Sleep-Ctrl and Wake-Ctrl had no significant between-session changes (p values > .05). Postsleep improvement in FA in Sleep-Dep correlated with longer stage 2 sleep (r(20) = 0.788, pfdr < .001) and stage 2 fast spindle number at O1 (r(18) = 0.692, pfdr = .015). CONCLUSIONS: Sleep gain, particularly stage 2 sleep and related physiology, potentially enhances inhibitory control ability responding to emotional information among individuals with depressive disorders.
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Trastorno Depresivo , Trastornos del Sueño-Vigilia , Adolescente , Adulto , Afecto , Depresión/psicología , Emociones , Femenino , Humanos , Masculino , Polisomnografía , Sueño , Trastornos del Sueño-Vigilia/psicología , Adulto JovenRESUMEN
Several chemotherapy agents have shown efficacy in the treatment of mycosis fungoides (MF). In the literature, there is limited data on the use of single agent etoposide for MF. We aimed to retrospectively review our experience with single agent etoposide in the treatment of advanced-stage or refractory early-stage MF with focus on analyzing its efficacy and safety. We included 13 MF patients who were treated with single agent etoposide. Patients were identified through the Cutaneous T Cell Lymphoma Database of Indiana University that involves patients treated from 2006 to 2016. Overall nine patients (69%) responded to treatment. No complete response was identified. Median time to response was 12.5 weeks (range: 6-25.4). Median duration of response was 43 weeks (range: 5-60) and median time to treatment failure was 31.3 weeks (range: 12.4-230). Hematological toxicity was observed in eight patients including two patients with grade 4 neutropenia and/or lymphopenia leading to sepsis. Higher doses of etoposide were significantly correlated with higher grades of anemia, neutropenia or lymphopenia (p < .05). Our study demonstrates that etoposide is an effective treatment for MF and may be considered in selected patients with progressive MF who have failed other treatments.
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Antineoplásicos Fitogénicos/uso terapéutico , Etopósido/uso terapéutico , Micosis Fungoide/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/efectos adversos , Bases de Datos Factuales , Etopósido/efectos adversos , Femenino , Humanos , Indiana , Masculino , Persona de Mediana Edad , Micosis Fungoide/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Woringer-Kolopp disease, also known as localized pagetoid reticulosis, is a rare cutaneous lymphoproliferative disorder classified as a solitary variant of mycosis fungoides (MF). Despite the indolent and benign nature of the disease, misdiagnosis and inappropriate treatment may result in years of debilitating symptoms and even loss of function. We present the case of a patient with long-standing Woringer-Kolopp disease that mimicked foot dermatitis. Histopathologic examination demonstrated epidermotropic infiltration of atypical lymphocytes that were CD3+ CD4- CD8-. The patient was successfully treated with topical keratolytics and bexarotene gel 1% with minimal residual lesions after 8 years of follow-up. We discuss the characteristics of this rare disease in contrast with localized MF as well as more aggressive forms of epidermotropic T-cell lymphoma.
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Dermatosis del Pie/diagnóstico , Reticulosis Pagetoide/patología , Neoplasias Cutáneas/patología , Anciano , Anticarcinógenos/uso terapéutico , Bexaroteno , Complejo CD3/metabolismo , Fármacos Dermatológicos/uso terapéutico , Diagnóstico Diferencial , Humanos , Masculino , Reticulosis Pagetoide/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Linfocitos T/metabolismo , Tetrahidronaftalenos/uso terapéutico , Urea/uso terapéuticoRESUMEN
The clinical course and outcome of malignant melanoma (MM) are well-established for immunocompetent groups; however, they are not well-documented for immunosuppressed populations. Specifically, the influence of immunosuppression may result in poorer outcomes, especially in more advanced cases of melanoma. We report a 67-year-old woman who had previously undergone a kidney and pancreas transplant and presented with American Joint Committee on Cancer (AJCC) stage IIIA melanoma with subsequent rapid demise. As medicine advances with greater numbers of organ transplant recipients, a multi-institutional prospective study for this at-risk population would be greatly beneficial to help characterize the incidence, progression, and prognosis of melanoma in posttransplant immunosuppressed populations.
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Trasplante de Riñón , Melanoma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Anciano , Diabetes Mellitus , Diagnóstico Diferencial , Femenino , Antebrazo , Humanos , Melanoma/etiología , Melanoma/patología , Melanoma/cirugía , Estadificación de Neoplasias , Insuficiencia Renal , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugíaRESUMEN
The municipality of Romblon in the Philippines is an island known for its marble industry. The subsurface of the Philippines is known for its limestone. The production of marble into slab, tiles, and novelty items requires heavy equipment to cut rocks and boulders. The finishing of marble requires polishing to smoothen the surface. During the manufacturing process, massive amounts of particulates and slurry are produced, and with a lack of technology and human expertise, the environment can be adversely affected. Hence, this study assessed and monitored the environmental conditions in the municipality of Romblon, particularly the soils and sediments, which were affected due to uncontrolled discharges and particulates deposition. A total of fifty-six soil and twenty-three sediment samples were collected and used to estimate the metal and metalloid (MM) concentrations in the whole area using a neural network-particle swarm optimization inverse distance weighting model (NN-PSO). There were nine MMs; e.g., As, Cr, Ni, Pb, Cu, Ba, Mn, Zn and Fe, with significant concentrations detected in the area in both soils and sediments. The geo-accumulation index was computed to assess the level of contamination in the area, and only the soil exhibited contamination with zinc, while others were still on a safe level. Nemerow's pollution index (NPI) was calculated for the samples collected, and soil was evaluated and seen to have a light pollution level, while sediment was considered as "clean". Furthermore, the single ecological risk (Er) index for both soil and sediment samples was considered to be a low pollution risk because all values of Er were less than 40.
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Head and neck cutaneous melanomas pose many treatment challenges. Intratumoral injectables offer local and possibly systemic therapy in unresectable lesions. Talimogene laherparepvec, an injectable oncolytic type 1 herpes simplex virus, can improve durable response rates compared with systemic granulocyte-macrophage colony-stimulating factor therapy in patients with stage IIIB to IVM1a unresectable melanoma. These benefits were most noticed in lower-stage subsets and treatment naive patients. Efficacy of talimogene laherparepvec was maintained in patients with head and neck melanoma. Talimogene laherparepvec plus systemic immunotherapies is being studied, with promising preliminary data. Numerous ongoing clinical trials are investigating other viral and nonviral injectables.
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Melanoma , Viroterapia Oncolítica , Neoplasias Cutáneas , Humanos , Inmunoterapia , Melanoma/terapia , Neoplasias Cutáneas/terapia , Resultado del TratamientoRESUMEN
Nocardiosis remains a fairly uncommon disease in the United States. Cutaneous nocardiosis is one of many infections that can spread in a sporotrichoid pattern and therefore can be difficult to diagnose without a high index of suspicion. It is mainly caused by Nocardia asteroides and Nocardia brasiliensis, with N brasiliensis isolated in most cases of lymphocutaneous nocardiosis. We present a case of lymphocutaneous nocardiosis in a 65-year-old immunosuppressed man and review the literature.
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Huésped Inmunocomprometido , Nocardiosis/diagnóstico , Enfermedades Cutáneas Bacterianas/diagnóstico , Anciano , Diagnóstico Diferencial , Humanos , Enfermedades Linfáticas/diagnóstico , Enfermedades Linfáticas/tratamiento farmacológico , Masculino , Nocardiosis/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/tratamiento farmacológicoRESUMEN
The deliberate use of chemical, biological, radiological, and nuclear (CBRN) materials in war or terrorist attacks is perceived as a great threat globally. In the event of a release of CBRN agents, protection by means of medical countermeasures (MedCMs) could reduce health vulnerability. Nonetheless, for some diseases caused by these agents, innovative MedCMs do not exist and many of those that do might not be readily available. Inappropriate research and development funding and government procurement efforts can result in adverse economic consequences (eg, lost income, cost per loss of life, medical expenses) far exceeding the costs of strong and comprehensive preparedness initiatives. By illustrating factors of demand-side rationale for CBRN MedCMs, this article aims to strengthen integrity of policy-making associated with current demand requirements. Namely, an approach to inspire broader assessment is outlined by compiling and adapting existing economic models and concepts to characterize both soft and hard factors that influence demand-side rationale. First, the soft factor context is set by describing the impact of behavioral and political economics. Then, lessons learned from past public health funding models and associated collaborative access infrastructure are depicted to represent hard factors that can enhance the viability of MedCM preparedness evaluations.
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Contramedidas Médicas , Terrorismo , Bioterrorismo , HumanosRESUMEN
We assessed the effect of a daytime sleep opportunity on planning and risk-related decision-making in emerging adults using multiple neurobehavioral assessments. A total of 136 healthy emerging adults (20.0 ± 1.5 years), 65% female, performed the Risky-Gains Task and the Tower of London test twice. Between these assessments, they were randomized to either have a sleep opportunity monitored by polysomnography (Sleep group, n = 101) or to stay awake (Wake group, n = 35). During Test 2, in comparison to the Sleep group, the Wake group showed increased sleepiness, worse planning ability and more decrease in reaction times when selecting risky choices. Changes in Tower of London test steps used and Risky-Gains Task response time correlated with the number of central and frontal fast sleep spindles, respectively. These results indicate that among emerging adults who commonly have poor sleep patterns, a daytime sleep opportunity was related to better planning ability, better psychomotor vigilance and stable response speeds in risk-related decision-making. Changes in planning and risk-related decision-making correlated with the number of sleep spindles during the nap, supporting a specific role for sleep in modulating planning and potentially other higher-order cognitive functions.
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Cognición/fisiología , Sueño/fisiología , Adolescente , Femenino , Humanos , Masculino , Polisomnografía/métodos , Tiempo de Reacción/fisiología , Asunción de Riesgos , Vigilia/fisiología , Adulto JovenRESUMEN
BACKGROUND: CD8+ lymphomatoid papulosis is frequently indistinguishable histopathologically from primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma except for the expression of CD30. However, absent or weak expression of CD30 has been rarely reported in cases of CD8+ LyP. OBJECTIVE: We aim to study the clinical and pathologic features of cases of CD8+ LyP with no or minimal expression of CD30. MATERIAL AND METHODS: We identified all cases of CD8+ LyP diagnosed in our institution over a period of 10 years. Blinded comparison of clinical and histopathologic features of cases with and without CD30 expression was performed. RESULTS: Among seven cases (four patients) with definitive clinical and histopathologic diagnosis of CD8+ LyP, two cases (29%) had no expression of CD30. These two cases had more prominent epidermotropism, less epidermal ulceration, and less vascular damage relative to cases with CD30 expression and therefore resembled mycosis fungoides and type B LyP. CD5 and CD7 were frequently lost regardless of the CD30 status. Expression of cytotoxic markers was not different between the two groups. In the two cases with lack of CD30 expression, subsequent biopsies showed classic features of CD8+ LyP with strong expression of CD30. CONCLUSION: CD8+ LyP with lack of expression of CD30 may have distinct histopathologic features that resemble mycosis fungoides and LyP type B. Clinically, they are indistinguishable from their CD30+ counterparts, signifying the importance of clinical correlation to avoid the erroneous diagnosis of lymphoma. Interval biopsies may be needed to establish a definitive diagnosis.
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Linfocitos T CD8-positivos/inmunología , Antígeno Ki-1/metabolismo , Papulosis Linfomatoide/diagnóstico , Micosis Fungoide/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adulto , Biopsia , Diagnóstico Diferencial , Femenino , Humanos , Papulosis Linfomatoide/inmunología , Papulosis Linfomatoide/patología , Masculino , Persona de Mediana Edad , Micosis Fungoide/inmunología , Micosis Fungoide/patología , Piel/citología , Piel/inmunología , Piel/patología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patologíaRESUMEN
Objective: To examine how risk-related decision making might be associated with habitual sleep variables, including sleep variability, sleep duration and perceived sleep need in young adults cross-sectionally and longitudinally. Design: 166 participants completed a 7-day protocol with sleep and risk-related decision-making measures at baseline (T1) and 12 months later (T2). Results: Habitual short sleep duration (averaging < 6 h nightly) was identified in 11.0% in our sample. After controlling for baseline demographic factors and risk-taking measures, self-reported sleep need at T1 interacted with habitual short sleep in predicting risk taking at follow-up (F8,139=9.575, adjusted R2=.431, p<.001). T1 greater perceived sleep need predicted more risk taking among short sleepers, but decreased risk taking among normal sleepers at T2. Variable sleep timing was cross-sectionally correlated with making more Risky choices at baseline and fewer Safe choices after loss at follow up. Conclusions: Young adults with variable sleep timing and those with short sleep duration coupled with high perceived sleep need were more likely to take risks. The moderating effects of perceived sleep need suggest that individual differences may alter the impact of sleep loss and hence should be measured and accounted for in future studies.
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Toma de Decisiones , Asunción de Riesgos , Sueño , Adolescente , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Masculino , Autoinforme , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: The Sleep Condition Indicator (SCI) and Insomnia Severity Index (ISI) are commonly used instruments to assess insomnia. We evaluated their psychometric properties, particularly their discriminant validity against structured clinical interview (according to DSM-5 and ICSD-3), and their concurrent validity with measures of sleep and daytime functioning. METHODS: A total of 158 young adults, 16% of whom were diagnosed with DSM-5 insomnia disorder and 13% with ICSD-3 Chronic Insomnia by structured interview, completed the ISI and SCI twice in 7-14 days, in addition to measures of sleep and daytime function. RESULTS: The Chinese version of the SCI was validated with good psychometric properties (ICC = 0.882). A cutoff of ≥8 on the ISI, ≤5 on the SCI short form, and ≤21 on the SCI achieved high discriminant validity (AUC > 0.85) in identifying individuals with insomnia based on both DSM-5 and ICSD-3 criteria. The SCI and ISI had comparable associations with subjective (0.18 < r < 0.51) and actigraphic sleep (0.31 < r < 0.43) and daytime functioning (0.34 < r < 0.53). CONCLUSION: The SCI, SCI short form, and ISI were found to correctly identify individuals with DSM-5- and ICSD-3-defined insomnia disorder. Moreover, they showed good concordance with measures of daytime dysfunction, as well as subjective and objective sleep. The SCI and ISI are recommended for use in clinical and research settings.