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1.
Appl Radiat Isot ; 201: 111028, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37748216

RESUMO

A network of specialist laboratories support the International Monitoring System (IMS) of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) with re-measurements of radionuclide samples, including xenon gas. The measurement of four xenon fission product radionuclides (133Xe, 135Xe, 131mXe and 133mXe) can be used to detect an underground nuclear explosion. Laboratories use a range of techniques to measure the radionuclides, including beta-gamma (ß-γ) coincidence spectrometry. These highly-sensitive measurements are capable of detecting concentrations of down to 500 atoms of 133Xe in a few cm3 of xenon. In some detector systems, detection of the metastable isomers (131mXe and 133mXe) can be more challenging due to interferences between the signatures of different radionuclides. Recent work has shown that using high-purity Germanium (HPGe) high-resolution gamma detectors, these interferences can be reduced, lowering the dependence of the detection limits on radionuclide sample isotopic composition. One downside of these detectors is the reduction in detection efficiency, which impacts the overall detection sensitivity; so assessing different detector systems is a priority for radionuclide laboratories. This work presents a coincidence detector system comprising of a plastic scintillator gas cell and a large-crystal high-purity germanium detector. The energy resolution, coincidence detection efficiency, MDA and interference factors are determined from measurements of synthetic radioxenon gas samples.

2.
Conserv Biol ; 37(5): e14090, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37246556

RESUMO

To understand the scope and scale of the loss of biodiversity, tools are required that can be applied in a standardized manner to all species globally, spanning realms from land to the open ocean. We used data from the International Union for the Conservation of Nature Red List to provide a synthesis of the conservation status and extinction risk of cetaceans. One in 4 cetacean species (26% of 92 species) was threatened with extinction (i.e., critically endangered, endangered, or vulnerable) and 11% were near threatened. Ten percent of cetacean species were data deficient, and we predicted that 2-3 of these species may also be threatened. The proportion of threatened cetaceans has increased: 15% in 1991, 19% in 2008, and 26% in 2021. The assessed conservation status of 20% of species has worsened from 2008 to 2021, and only 3 moved into categories of lesser threat. Cetacean species with small geographic ranges were more likely to be listed as threatened than those with large ranges, and those that occur in freshwater (100% of species) and coastal (60% of species) habitats were under the greatest threat. Analysis of odontocete species distributions revealed a global hotspot of threatened small cetaceans in Southeast Asia, in an area encompassing the Coral Triangle and extending through nearshore waters of the Bay of Bengal, northern Australia, and Papua New Guinea and into the coastal waters of China. Improved management of fisheries to limit overfishing and reduce bycatch is urgently needed to avoid extinctions or further declines, especially in coastal areas of Asia, Africa, and South America.


Estado en la lista roja y riesgo de extinción de las ballenas, delfines y marsopas del mundo Resumen Para comprender el alcance y la escala de la pérdida de biodiversidad, se necesitan herramientas que puedan aplicarse de forma estandarizada a todas las especies a nivel mundial y que abarquen todos los ámbitos desde la tierra hasta el océano. Utilizamos datos de la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza para proporcionar una síntesis del estado de conservación y el riesgo de extinción de los cetáceos. Una de cada 4 especies de cetáceos (26% de 92 especies) se encuentra amenazada (es decir, en peligro crítico, en peligro o vulnerable) y el 11% de las especies está clasificado como casi amenazada. El 10% de las especies de cetáceos carecía de datos, por lo que predijimos que 2-3 de estas especies también podrían estar amenazadas. La proporción de cetáceos amenazados ha aumentado: 15% en 1991, 19% en 2008 y 26% en 2021. El estado de conservación evaluado del 20% de las especies ha empeorado de 2008 a 2021, pues sólo 3 pasaron a categorías de menor amenaza. Las especies de cetáceos con áreas de distribución geográficas pequeñas tenían más probabilidades de ser catalogadas como amenazadas que aquellas con áreas de distribución extensas, y aquellas que ocurren en hábitats de agua dulce (100% de las especies) y costeros (60% de las especies) eran las que se encontraban bajo mayor amenaza. La superposición de los mapas de distribución de las especies reveló la existencia de puntos calientes de pequeños cetáceos amenazados en el sudeste asiático y en una zona que abarca el Triángulo de Coral y se extiende por las aguas cercanas a la costa de la Bahía de Bengala, el norte de Australia, Papúa Nueva Guinea y las aguas costeras de China. Urge mejorar la gestión de las pesquerías para limitar la sobrepesca y reducir la captura accesoria con el fin de evitar extinciones o mayores descensos, especialmente en las zonas costeras de Asia, África y Sudamérica.


Assuntos
Golfinhos , Toninhas , Animais , Conservação dos Recursos Naturais , Extinção Biológica , Baleias , Pesqueiros , Biodiversidade , Espécies em Perigo de Extinção
3.
Clin Oncol (R Coll Radiol) ; 35(3): 188-198, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36610878

RESUMO

AIMS: To evaluate the safety and effectiveness of oxaliplatin-based combination chemotherapy for patients with metastatic colorectal cancer (mCRC) to extrahepatic sites. MATERIALS AND METHODS: We conducted a population-based retrospective study examining the safety and effectiveness of perioperative oxaliplatin for resectable or potentially resectable colorectal metastases in Ontario, Canada. Outcomes were also compared with patients with liver-only metastases. Patients received oxaliplatin for mCRC between 1 January 2013 and 30 June 2020. RESULTS: In total, 192 patients had extrahepatic metastases. Seventy per cent had R0 metastasectomy. The 3-year disease-free survival and overall survival were 62% and 79%, respectively; <4% of patients died within 60 days of metastasectomy and 74-90% of patients received treatment according to recommendations from a multidisciplinary setting. Compared with liver-only controls (n = 1306), patients had mCRC to the lung only (n = 115), lung and liver (n = 55) and liver with non-pulmonary site (n = 22). Extrahepatic metastases were more likely to be found for patients whose primary colorectal resection had positive margins (14% versus 7%, P = 0.005) and primary tumours located in the rectum [odds ratio 4.01 (2.31-6.97)]. After adjustment, there was no difference in overall survival between liver-only controls and patients with lung-only [hazard ratio 0.82 (0.59-1.15)] or liver and lung metastases [hazard ratio 1.26 (0.85-1.87)] (P = 0.24). In total, 79/115 (69%) of patients with lung-only metastases had a metastasectomy compared with 645/1306 (49%) and 15/55 (27%) of patients with liver-only and liver and lung metastases, respectively. Hospital visits were similar between patients with liver-only and extrahepatic metastases. CONCLUSION: Oxaliplatin-based chemotherapy for patients with resectable or potentially resectable mCRC with extrahepatic metastases was safe and resulted in similar outcomes in appropriately selected patients when compared with patients with liver-only metastases.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias Retais , Humanos , Oxaliplatina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Estudos Retrospectivos , Estudos de Coortes , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Ontário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
4.
Geohealth ; 7(1): e2022GH000699, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36618584

RESUMO

Windblown dust impacts human health, air quality, and climate. The National Weather Service Storm Events Database (SED) is a widely used dataset of significant or unusual weather, including dust storms (DS), and resulting deaths, injuries, and material losses in the USA. The SED is frequently used by medical, social, and atmospheric scientists. However, it is uncertain whether this dataset reliably represents spatial and temporal variations and trends of DS. Analyzing the SED from 2000 to 2020 identified 1,167 DS reports; removing reports of the same event from multiple locations left 647 DS in 21 USA states. The number of DS ranged from 12 in 2008 to 53 in 2018, with no strong interannual trends detected (R 2 was 0.3). By examining the DS events reported in the SED based on meteorological observations including wind speed, visibility, and weather codes, we determined that the SED was not only missing many DS (visibility <1 km), but also included many blowing dust (BLDU) events. 49.9% of 491 reported DS events in SED had visibility >1 km and were incorrectly reported as DS. Underrepresentation of DS and inclusion of BLDU may be partially due to the diverse sources contributing to the SED and a lack of verification of the reports and their consistency. Although the SED is an extremely useful and valuable database of impactful weather, including DS, the issues found in this study warrant caution in use of this dataset for many geohealth applications.

5.
Cell Rep ; 36(12): 109727, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34551293

RESUMO

In traumatic brain injury (TBI), a diversity of brain resident and peripherally derived myeloid cells have the potential to worsen damage and/or to assist in healing. We define the heterogeneity of microglia and macrophage phenotypes during TBI in wild-type (WT) mice and Ccr2-/- mice, which lack macrophage influx following TBI and are resistant to brain damage. We use unbiased single-cell RNA sequencing methods to uncover 25 microglia, monocyte/macrophage, and dendritic cell subsets in acute TBI and normal brains. We find alterations in transcriptional profiles of microglia subsets in Ccr2-/- TBI mice compared to WT TBI mice indicating that infiltrating monocytes/macrophages influence microglia activation to promote a type I IFN response. Preclinical pharmacological blockade of hCCR2 after injury reduces expression of IFN-responsive gene, Irf7, and improves outcomes. These data extend our understanding of myeloid cell diversity and crosstalk in brain trauma and identify therapeutic targets in myeloid subsets.


Assuntos
Lesões Encefálicas Traumáticas/patologia , Microglia/metabolismo , Receptores CCR2/genética , Animais , Antígenos Ly/genética , Antígenos Ly/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas Traumáticas/metabolismo , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Fator Regulador 7 de Interferon/genética , Fator Regulador 7 de Interferon/metabolismo , Interferon Tipo I/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/citologia , Monócitos/citologia , Monócitos/metabolismo , Receptores CCR2/antagonistas & inibidores , Receptores CCR2/deficiência , Receptores CCR2/metabolismo
6.
Eur J Prosthodont Restor Dent ; 29(4): 209-217, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33770422

RESUMO

Cracked tooth syndrome (CTS) is a common presentation in general practice. The diagnosis and management of teeth with CTS may be difficult due to the unknown extent of the crack. This article reviews the aetiology, diagnosis, management and prognosis of teeth with CTS. A thorough examination is required to effectively assess CTS. Intervention should aim to relieve symptoms and brace the remaining tooth structure effectively against further flexion. Restored teeth with CTS have a guarded prognosis due to the risk of further crack propagation, but the chances of survival at 5-years is acceptable (74.1-96.8%).


Assuntos
Síndrome de Dente Quebrado , Síndrome de Dente Quebrado/diagnóstico , Síndrome de Dente Quebrado/terapia , Humanos , Prognóstico
7.
J Biol Chem ; 296: 100469, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33639169

RESUMO

Alterations in mitochondrial fission may contribute to the pathophysiology of several neurodegenerative diseases, including Alzheimer's disease (AD). However, we understand very little about the normal functions of fission or how fission disruption may interact with AD-associated proteins to modulate pathogenesis. Here we show that loss of the central mitochondrial fission protein dynamin-related protein 1 (Drp1) in CA1 and other forebrain neurons markedly worsens the learning and memory of mice expressing mutant human amyloid precursor protein (hAPP) in neurons. In cultured neurons, Drp1KO and hAPP converge to produce mitochondrial Ca2+ (mitoCa2+) overload, despite decreasing mitochondria-associated ER membranes (MAMs) and cytosolic Ca2+. This mitoCa2+ overload occurs independently of ATP levels. These findings reveal a potential mechanism by which mitochondrial fission protects against hAPP-driven pathology.


Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Dinaminas/metabolismo , Dinâmica Mitocondrial/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/metabolismo , Região CA1 Hipocampal/metabolismo , Cálcio/metabolismo , Modelos Animais de Doenças , Dinaminas/genética , Dinaminas/fisiologia , Feminino , Hipocampo/metabolismo , Humanos , Aprendizagem/fisiologia , Masculino , Memória/fisiologia , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/genética , Neurônios/metabolismo , Fosforilação
8.
J Nutr Health Aging ; 24(4): 438-444, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32242212

RESUMO

The Precipitating Events Project (PEP Study) is an ongoing longitudinal study of 754 nondisabled community-living persons age 70 years or older who were members of a large health plan in greater New Haven, Connecticut, USA. The study was established to rigorously evaluate the epidemiology of disability in older persons and to elucidate the role of intervening illnesses and injuries on the disabling process. Of the eligible members, 75.2% agreed to participate and were enrolled between March 1998 and October 1999. Participants have completed comprehensive home-based assessments at 18-month intervals and have been interviewed monthly over the phone with a completion rate of 99%. Detailed participant-level data on health care utilization are obtained annually through linkages with Medicare claims. Through June 2019, 702 (93.1%) participants have died after a median of 109 months, while 43 (5.7%) have dropped out of the study after a median of 27 months. Death certificates are available for all decedents. To date, 117 original reports have been published using data from the PEP Study, including many focusing on other high priority areas such as end of life, frailty, depressive symptoms, aging stereotypes, pain, sleep, and methodologic research. The PEP Study welcomes proposals to access data for meritorious analyses from qualified investigators.


Assuntos
Atividades Cotidianas/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos
9.
Cell Rep ; 30(2): 381-396.e4, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31940483

RESUMO

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Ciclopropanos/farmacologia , Epilepsias Mioclônicas/tratamento farmacológico , Nitrilas/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Tiazóis/farmacologia , Regulação Alostérica/efeitos dos fármacos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Células CHO , Cricetulus , Modelos Animais de Doenças , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pirazóis/farmacologia , Receptores de N-Metil-D-Aspartato/agonistas
10.
Gerontechnology ; 19(Suppl 1)2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33574738

RESUMO

PURPOSE: It is estimated that 15.7% of people aged 60 years and older were subjected to some form of Elder Mistreatment (EM) globally (Yon et al., 2017). In the USA, as many as 1 in 24 EM cases are left unidentified by professionals, with a 300% increased mortality risk for older adults who do not receive help (National Center on Elder Abuse, n.d.; Dong, 2009). Current methods of screening tend to miss less obvious signs of EM and may discourage older adults from disclosing EM, due to either a lack of understanding of what constitutes mistreatment or fear of retaliation from the perpetrator. METHOD: Our approach shifts the focus of EM identification to the older adults themselves through an automated tablet-based tool. The Virtual cOaching in making Informed Choices on Elder Mistreatment Self-Disclosure (VOICES) tool includes various multimedia components such as videos, audio, and animations designed to educate and enhance screening. Patients screened as positive are guided through a Brief Negotiated Interview (BNI) utilizing motivational interviewing to assist in self-identification (recognize that they are experiencing elder mistreatment) or self-disclosure (inform others about their elder mistreatment experiences). During tool development, we conducted a qualitative study to evaluate the perceived value and likelihood of adopting a tablet-based approach to facilitate screening and self-disclosure of EM in the ED. We held 3 focus groups with stakeholders, including 24 adults 60 years or over, 2 social workers, 2 caregivers, and 2 ED clinicians. We used the findings from the focus groups and User-Centered Design approach (UCD) to develop the tablet-based screening tool. Once the tool was ready, we tested its usability and acceptability with 14 older adults. RESULTS AND DISCUSSION: Focus group participants supported use of a tablet-based tool to screen for EM, indicating that digital screening benefits from feelings of privacy and anonymity. On a 7-point Likert scale ranging from "1=Very Comfortable" to "7=Very Uncomfortable", older adults scored 2.8 on average for whether they would feel comfortable using a tablet device to screen for EM. Prominent suggestions made by older adults included using a female voice for the tool narrator, larger font size, more multimedia, headphones for privacy; and having someone available during screening for assistance if needed. Participants indicated that it is difficult for older adults experiencing EM to ask for help and that any type of mistreatment screening would be helpful. They also highlighted the need to explain community resources available to older adults once EM is disclosed, especially resources offering help to the caregiver. Participants of the usability evaluation rated the tool a mean score of 86.6 (median= 88.8, iQR =18.1) on the System Usability Scale (SUS), far above the benchmark SUS score of 68, which indicates that the system is "good" or "acceptable" (Bangor et al., 2008). Shifting the focus from the provider to the older adult may encourage self-disclosure of EM by addressing major barriers to traditional screening processes. In summary, this study supported the use of self-administered automated tablet-based screening for EM. Participants generally believed that the use of digital health tools to facilitate the screening process would be beneficial in the ED setting.

11.
Freshw Biol ; 64(7): 1303-1314, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31787787

RESUMO

1. Dry, ephemeral, desert wetlands are major sources of windblown sediment, as well as repositories for diapausing stages (propagules) of aquatic invertebrates. Zooplankton propagules are of the same size range as sand and dust grains. They can be deflated and transported in windstorm events. This study provides the evidence that dust storms aid in dispersal of microinvertebrate propagules via anemochory (aeolian transport). 2. We monitored 91 windstorms at six sites in the southwestern U.S. over a 17-year period. The primary study site was located in El Paso, Texas in the northern Chihuahuan Desert. Additional samples were collected from the Southern High Plains region. Dust carried by these events was collected and rehydrated to hatch viable propagules transported with it. 3. Using samples collected over a six-year period, 21 m above the ground which included 59 storm events, we tested the hypothesis that transport of propagules is correlated with storm intensity by monitoring meteorological conditions such as storm duration, wind direction, wind speed, and PM10 (fine dust concentration). An air quality monitoring site located adjacent to the dust samplers provided quantitative hourly measurements. 4. Rehydration results from all events showed that ciliates were found in 92% of the samples, rotifers in 81%, branchiopods in 29%, ostracods in 4%, nematodes in 13%, gastrotrichs in 16%, and tardigrades in 3%. Overall, four bdelloid and 11 monogonont rotifer species were identified from rehydrated windblown dust samples. 5. PCA results indicated gastrotrichs, branchiopods, nematodes, tardigrades, and monogonont rotifer occurrence positively correlated with PM10 and dust event duration. Bdelloid rotifers were correlated with amount of sediment deposited. NMDS showed a significant relationship between PM10 and occurrence of some taxa. Zero-inflated, general linear models with mixed-effects indicated significant relationships with bdelloid and nematode transport and PM10. 6. Thus, windstorms with high particulate matter concentration and long duration are more likely to transport microinvertebrate diapausing stages in drylands.

12.
Opt Express ; 27(16): 23164-23172, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510599

RESUMO

We demonstrate a significant enhancement in the sensitivity of split ring resonator terahertz metamaterial dielectric sensors by the introduction of etched trenches into their inductive-capacitive gap area, both through finite element simulations and in experiments performed using terahertz time-domain spectroscopy. The enhanced sensitivity is demonstrated by observation of an increased frequency shift in response to overlaid dielectric material of thicknesses up to 18 µm deposited on to the sensor surface. We show that sensitivity to the dielectric is enhanced by a factor of up to ∼2.7 times by the incorporation of locally etched trenches with a depth of ∼3.4 µm, for example, and discuss the effect of the etching on the electrical properties of the sensors. Our experimental findings are in good agreement with simulations of the sensors obtained using finite element methods.

13.
J Neurosci ; 39(36): 7102-7117, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31320449

RESUMO

The lateral septum (LS) plays an important role in regulating aggression. It is well recognized that LS lesions lead to a dramatic increase in aggressive behaviors. A better understanding of LS neurophysiology and its functional output is therefore important to assess LS involvement in regulating aggression. The LS is a heterogeneous structure that maintains inputs and outputs with multiple brain regions, and is also divided into subregions that innervate one another. Thus, it is challenging to identify the exact cell type and projections for characterization. In this study, we determined the expression pattern of the calcium-activated chloride channel, TMEM16B, in the LS of both male and female mice. We then investigated the physiological contribution of the calcium-activated chloride channel to LS neuronal signaling. By performing whole-cell patch-clamp recording, we showed that TMEM16B alters neurotransmitter release at the hippocampal-LS synapse, and regulates spike frequency and spike frequency adaptation in subpopulations of LS neurons. We further demonstrated that loss of TMEM16B function promotes lengthened displays of aggressive behaviors by male mice during the resident intruder paradigm. In conclusion, our findings suggest that TMEM16B function contributes to neuronal excitability in subpopulations of LS neurons and the regulation of aggression in male mice.SIGNIFICANCE STATEMENT Aggression is a behavior that arose evolutionarily from the necessity to compete for limited resources and survival. One particular brain region involved in aggression is the lateral septum (LS). In this study, we characterized the expression of the TMEM16B calcium-activated chloride channel in the LS and showed that TMEM16B regulates the action potential firing frequency of LS neurons. We discovered that loss of TMEM16B function lengthens the displays of aggressive behaviors in male mice. These findings suggest that TMEM16B plays an important role in regulating LS neuronal excitability and behaviors associated with LS function, thereby contributing to our understanding of how the LS may regulate aggression.


Assuntos
Potenciais de Ação , Agressão , Anoctaminas/metabolismo , Núcleos Septais/fisiologia , Animais , Anoctaminas/genética , Feminino , Hipocampo/citologia , Hipocampo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neurônios/fisiologia , Núcleos Septais/citologia , Núcleos Septais/metabolismo , Fatores Sexuais , Sinapses/metabolismo , Sinapses/fisiologia , Potenciais Sinápticos
14.
Colorectal Dis ; 21(7): 833-840, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30897258

RESUMO

AIM: Restoration of bowel continuity after Hartmann's procedure (RoH) can be challenging and associated with considerable morbidity. A technique using single-incision laparoscopic surgery through the stoma site (SIL RoH) has been shown to be feasible and safe. In this study, we compared clinical outcomes of SIL RoH with conventional laparoscopic surgery (CL) and open surgery (OS). METHODS: This was a retrospective analysis of a prospectively maintained database between 2007 and 2017 in a UK colorectal unit. The access technique was decided by the surgeon on a case by case basis. RESULTS: A total of 106 patients underwent RoH. It was carried out for diverticular disease (n = 71, 67.6%), cancer (n = 19, 17.9%) and anastomotic leak (n = 4, 3.8%). The remainder (n = 12, 11.3%) were for miscellaneous reasons including trauma. Most RoHs were performed via OS (n = 87, 81.1%). The most common intended approaches for RoH were SIL (n = 56, 52.8%) and OS (n = 34, 32.1%) with fewer starting with CL (n = 16, 15.1%). Conversion to OS took place in five (8.9%) patients with SIL and six (37.5%) with CL (P = 0.005). Postoperative complications occurred in 17 (30.4%) for SIL, seven (43.8%) for CL and 17 (50.0%) for OS (P = 0.162). Median operating time for SIL was 146 min (range 44-389), 211 min (109-320) for CL and 211 min (85-420) for OS (P < 0.001). Median length of stay was 4 days (2-44) for SIL compared to 6 (3-34) for CL and 7 (4-34) for OS (P < 0.001). Discharge on or before day 5 was achieved in 41 (74.5%) patients for SIL compared to six (37.5%) for CL and seven (20.6%) for OS (P < 0.001). CONCLUSION: Compared to OS and CL, SIL RoH appears to have shorter operating times and hospitalization, with no discernible difference in morbidity; this finding requires further evaluation in a randomized setting.


Assuntos
Colostomia/métodos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Proctocolectomia Restauradora/métodos , Estomas Cirúrgicos/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo/cirurgia , Bases de Dados Factuais , Feminino , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Proctocolectomia Restauradora/efeitos adversos , Estudos Prospectivos , Reto/cirurgia , Estudos Retrospectivos , Ferida Cirúrgica , Resultado do Tratamento , Reino Unido , Adulto Jovem
16.
Neuron ; 101(6): 1099-1108.e6, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30737131

RESUMO

Cerebrovascular alterations are a key feature of Alzheimer's disease (AD) pathogenesis. However, whether vascular damage contributes to synaptic dysfunction and how it synergizes with amyloid pathology to cause neuroinflammation and cognitive decline remain poorly understood. Here, we show that the blood protein fibrinogen induces spine elimination and promotes cognitive deficits mediated by CD11b-CD18 microglia activation. 3D molecular labeling in cleared mouse and human AD brains combined with repetitive in vivo two-photon imaging showed focal fibrinogen deposits associated with loss of dendritic spines independent of amyloid plaques. Fibrinogen-induced spine elimination was prevented by inhibiting reactive oxygen species (ROS) generation or genetic ablation of CD11b. Genetic elimination of the fibrinogen binding motif to CD11b reduced neuroinflammation, synaptic deficits, and cognitive decline in the 5XFAD mouse model of AD. Thus, fibrinogen-induced spine elimination and cognitive decline via CD11b link cerebrovascular damage with immune-mediated neurodegeneration and may have important implications in AD and related conditions.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Espinhas Dendríticas/metabolismo , Fibrinogênio/metabolismo , Microglia/metabolismo , Placa Amiloide/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Antígeno CD11b/metabolismo , Antígenos CD18/metabolismo , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Espinhas Dendríticas/patologia , Modelos Animais de Doenças , Humanos , Imageamento Tridimensional , Camundongos , Placa Amiloide/patologia , Espécies Reativas de Oxigênio/metabolismo
17.
Colorectal Dis ; 21(1): 79-89, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30260551

RESUMO

AIM: Single-incision laparoscopic (SIL) surgery is expanding, but its benefits, efficacy and safety compared with conventional laparoscopic (CL) surgery remain unclear. This pilot study examined clinical outcomes and biochemical markers of inflammation for colorectal resections by SIL and CL in a randomized controlled pilot trial. METHOD: Fifty patients undergoing elective colorectal resection were randomized to either SIL or CL. Primary outcomes were operating time and length of stay (LoS); secondary outcomes included combined length of scars, pain scores, complications, Quality of Life EQ5D-VAS and the inflammatory markers interleukin-6 (IL-6), IL-8 and C-reactive protein (CRP) at baseline, 2, 6, 24 and 72 h. RESULTS: There was no difference in age, gender, body mass index, indications and site of surgery, American Society of Anesthesiologists grade or incidence of previous surgery between the groups. Except for one conversion from SIL to open surgery, surgery was completed as intended. No difference between SIL and CL was found for operating time [median 130 (72-220) vs 130 (90-317) min, respectively, P = 0.528], LoS [median 4 (3-8) vs 4 (2-19)days, P = 0.888] and time to first flatus [2 (1-4) vs 2 (1-5) days, P = 0.374]. The combined length of scars was significantly shorter for SIL [4 (2-18) vs 7 (5-8) cm, P < 0.001]; in each group, four postoperative complications occurred (16%). Postoperative pain scores were similar [mean 7.67 (interquartile range 4) vs 7.25 (interquartile range 3.75), P = 0.835] to day 3. EQ5D-VAS was no different for both groups at discharge [72.5 (40-90) vs 70 (30-100), P = 0.673] but slightly higher for CL at 3 months [79 (45-100) vs 90 (50-100), P = 0.033].The IL-6, IL-8 and CRP levels between both groups showed similar peaks and no significant differences. CONCLUSION: SIL colorectal surgery by experienced laparoscopic surgeons appears to be safe and equivalent to CL, with no discernible difference in its effect on the physiological response to surgical trauma.


Assuntos
Colectomia/métodos , Neoplasias Colorretais/cirurgia , Doenças Diverticulares/cirurgia , Doenças Inflamatórias Intestinais/cirurgia , Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Duração da Cirurgia , Protectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/imunologia , Feminino , Humanos , Inflamação/imunologia , Interleucina-6/imunologia , Interleucina-8/imunologia , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/epidemiologia , Projetos Piloto , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Método Simples-Cego , Adulto Jovem
18.
Limnol Oceanogr Lett ; 3(4): 320-330, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30534597

RESUMO

While separated by large expanses of dry terrain unsuitable for aquatic biota, aridland waters possess high biodiversity. How aquatic micrometazoans disperse to, and colonize, these isolated ephemeral habitats are not well understood. We used a multi-faceted approach including wind tunnel and rehydration experiments, and next-generation sequencing to assess potential movement of diapausing propagules of aquatic invertebrates by anemochory across regional scales (102-105 km). Wind tunnel experiments using dry playa sediments with added micrometazoan propagules demonstrated that after entrainment by saltation and downwind transport were subsequently recoverable as viable animals when rehydrated. Further, rehydration of fallen natural dust yielded micrometazoans, including rotifers, gastrotrichs, microcrustaceans, and nematodes. Using conserved DNA primers, we identified >3,300 eukaryotic Operational Taxonomic Units (excluding fungi) in the dust including some taxa found in rehydration experiments. Thus, we provide strong evidence that anemochory can disperse micrometazoans among isolated, ephemeral ecosystems in North American deserts and likely elsewhere.

19.
J Nutr Health Aging ; 22(10): 1253-1258, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30498834

RESUMO

OBJECTIVES: Little is known about the severity and long-term health and economic consequences of sarcopenia. We developed a sarcopenia index to measure severity in older Americans and estimated the long-term societal benefits generated by effective interventions to mitigate severity. DESIGN: Using a micro-simulation model, we quantified the potential societal value generated in the US in 2010-2040 by reductions in sarcopenia severity in older adults. All analyses were performed in Stata and SAS. SETTING AND PARTICIPANTS: Secondary data from the National Health and Nutrition Examination Survey (NHANES) (N = 1634) and Health and Retirement Study (HRS) (N = 952) were used to develop a sarcopenia severity index in older adults. MEASUREMENTS: Multi-trait multi-method and factor analyses were used to validate and calibrate the sarcopenia severity index, which was modeled as a function of gait speed, walking without an assistive device, and moderate physical activity. RESULTS: In representative elderly populations, reducing sarcopenia severity by improving gait speed by 0.1 m/s in those with gait speed under 0.8 m/s generated a cumulative benefit of $65B by 2040 (2015 dollars). Improving walking ability in those with walking difficulty generated cumulative social benefit of $787B by 2040. CONCLUSIONS: Reducing sarcopenia severity would generate significant health and economic benefits to society-almost $800B in the most optimistic scenarios.


Assuntos
Sarcopenia/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Feminino , Humanos , Masculino , Limitação da Mobilidade
20.
BMC Musculoskelet Disord ; 19(1): 292, 2018 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-30115055

RESUMO

BACKGROUND: Musculoskeletal (MSK) conditions are common and the biggest global cause of physical disability. The objective of the current study was to estimate the population prevalence of MSK-related pain using a standardized global MSK survey module for the first time. METHODS: A MSK survey module was constructed by the Global Alliance for Musculoskeletal Health Surveillance Taskforce and the Global Burden of Disease MSK Expert Group. The MSK module was included in the 2015 Solomon Islands Demographic and Health Survey. The sampling design was a two-stage stratified, nationally representative sample of households. RESULTS: A total of 9214 participants aged 15-49 years were included in the analysis. The age-standardized four-week prevalence of activity-limiting low back pain, neck pain, and hip and/or knee pain was 16.8, 8.9, and 10.8%, respectively. Prevalence tended to increase with age, and be higher in those with lower levels of education. CONCLUSIONS: Prevalence of activity-limited pain was high in all measured MSK sites. This indicates an important public health issue for the Solomon Islands that needs to be addressed. Efforts should be underpinned by integration with strategies for other non-communicable diseases, aging, disability, and rehabilitation, and with other sectors such as social services, education, industry, and agriculture. Primary prevention strategies and strategies aimed at self-management are likely to have the greatest and most cost-effective impact.


Assuntos
Artralgia/epidemiologia , Dor Lombar/epidemiologia , Cervicalgia/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Artralgia/diagnóstico , Escolaridade , Feminino , Inquéritos Epidemiológicos , Humanos , Dor Lombar/diagnóstico , Masculino , Melanesia/epidemiologia , Pessoa de Meia-Idade , Cervicalgia/diagnóstico , Medição da Dor , Prevalência , Adulto Jovem
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