RESUMO
Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5-7. This hampers the accuracy of global land carbon-climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.
Assuntos
Respiração Celular , Ecossistema , Aquecimento Global , Tundra , Regiões Árticas , Carbono/metabolismo , Carbono/análise , Ciclo do Carbono , Conjuntos de Dados como Assunto , Concentração de Íons de Hidrogênio , Nitrogênio/metabolismo , Nitrogênio/análise , Plantas/metabolismo , Estações do Ano , Solo/química , Microbiologia do Solo , Temperatura , Fatores de TempoRESUMO
Widespread screening for hepatitis C virus (HCV) is necessary for Canada to meet its HCV elimination goals by 2030. People who currently or previously injected drugs are at high risk for HCV. Opioid agonist therapy (OAT, such as methadone and buprenorphine) has been shown to help stabilize the lives of people who are opioid-dependent. The distribution of OAT in North America typically requires daily, weekly, or monthly clinic visits and presents an opportunity for engagement, screening and treatment for those at high-risk of HCV. In this study, HCV screening was conducted by staff at OAT clinics in Ontario from 2016 to 2020 and those with chronic infections were treated on-site with direct-acting antivirals. Point-of-care or dried blood spot (DBS) testing was used for antibodies, DBS or serum for HCV RNA and serum for HCV RNA at SVR12 (sustained virological response). Clinics screened 1954 people (mean age 40 years ±12, 63% male). Forty-five percent were antibody positive, of whom 64% were HCV RNA+. Eighty percent of those RNA+ set an appointment in which 99% attended. Ninety-six percent started treatment with 87% completing treatment. Sixty-eight percent of people who completed treatment submitted a sample for SVR12 testing of which 97% achieved a virological cure. Results suggest that HCV screening and treatment at OAT clinics is feasible, effective and warrants expansion. Data suggest strong treatment adherence due to high rates of SVR12 comparable with other OAT-based HCV treatment programs. The lack of SVR12 sampling could be addressed by either on-site phlebotomy or incentivizing SVR12 sampling.
Assuntos
Hepatite C Crônica , Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Masculino , Adulto , Feminino , Hepacivirus/genética , Analgésicos Opioides/uso terapêutico , Antivirais , Ontário/epidemiologia , Prevalência , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , RNA , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Abuso de Substâncias por Via Intravenosa/tratamento farmacológicoRESUMO
OBJECTIVE: Type 2 diabetes (T2D) is characterised by the loss of first-phase insulin secretion. We studied mice with ß-cell selective loss of the glucagon receptor (Gcgrfl/fl X Ins-1Cre), to investigate the role of intra-islet glucagon receptor (GCGR) signalling on pan-islet [Ca2+]I activity and insulin secretion. METHODS: Metabolic profiling was conducted on Gcgrß-cell-/- and littermate controls. Crossing with GCaMP6f (STOP flox) animals further allowed for ß-cell specific expression of a fluorescent calcium indicator. These islets were functionally imaged in vitro and in vivo. Wild-type mice were transplanted with islets expressing GCaMP6f in ß-cells into the anterior eye chamber and placed on a high fat diet. Part of the cohort received a glucagon analogue (GCG-analogue) for 40 days and the control group were fed to achieve weight matching. Calcium imaging was performed regularly during the development of hyperglycaemia and in response to GCG-analogue treatment. RESULTS: Gcgrß-cell-/- mice exhibited higher glucose levels following intraperitoneal glucose challenge (control 12.7 mmol/L ± 0.6 vs. Gcgrß-cell-/- 15.4 mmol/L ± 0.0 at 15 min, p = 0.002); fasting glycaemia was not different to controls. In vitro, Gcgrß-cell-/- islets showed profound loss of pan-islet [Ca2+]I waves in response to glucose which was only partially rescued in vivo. Diet induced obesity and hyperglycaemia also resulted in a loss of co-ordinated [Ca2+]I waves in transplanted islets. This was reversed with GCG-analogue treatment, independently of weight-loss (n = 8). CONCLUSION: These data provide novel evidence for the role of intra-islet GCGR signalling in sustaining synchronised [Ca2+]I waves and support a possible therapeutic role for glucagonergic agents to restore the insulin secretory capacity lost in T2D.
Assuntos
Diabetes Mellitus Tipo 2 , Glucagon , Glucose , Homeostase , Secreção de Insulina , Células Secretoras de Insulina , Receptores de Glucagon , Transdução de Sinais , Animais , Glucagon/metabolismo , Camundongos , Células Secretoras de Insulina/metabolismo , Glucose/metabolismo , Receptores de Glucagon/metabolismo , Receptores de Glucagon/genética , Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo , Masculino , Ilhotas Pancreáticas/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Dieta Hiperlipídica , Glicemia/metabolismo , FemininoRESUMO
The Meningitis-Retention Syndrome associates aseptic meningitis and neurogenic bladder, with a vesical dysfunction that outlasts meningitis widely. Urodynamic assessment shows a detrusor palsy with normal function of the external sphincter. We report a 24-year-old male admitted for headache, fever, myalgias and acute urinary retention, which was diagnosed as a urinary tract infection. Worsening of symptoms and slight meningeal signs prompted for a lumbar puncture that yielded a cerebrospinal fluid with 94 lymphocytes, in which etiological evaluation was inconclusive. Meningeal syndrome and myalgia subsided by the fifth day, while urinary retention persisted. A magnetic resonance imaging of the brain and spinal cord done at the fifth day, showed high intensity signals in basal ganglia and central spinal cord, not altered by contrast. These images disappeared in the imaging control performed two months later. Bladder dysfunction lasted at least until the second month of follow up.
Assuntos
Humanos , Masculino , Adulto Jovem , Meningite Asséptica/complicações , Retenção Urinária/etiologia , Encéfalo/patologia , Imageamento por Ressonância Magnética , Meningite Asséptica/diagnóstico , Medula Espinal/patologia , Síndrome , Bexiga Urinaria Neurogênica/etiologiaRESUMO
Antecedentes: La nocardiosis es originada por distintas cepas de Nocardia, bacterias Gram positivas que afecta a humanos y animales. Pueden producir infecciones sistémicas de ingreso cutáneo o pulmonar, que llegan a comprometer el Sistema Nervioso Central. Se afectan especialmente pacientes inmunosuprimidos que pueden desarrollar abscesos cerebrales, visibles en la Resonancia Magnética (RM), pero que no expresan síntomas de las lesiones focales o son parvosintomáticos. Pacientes y Método: Queremos comunicar dos mujeres con trasplante renal en tratamiento inmunosupresor, que desarrollaron cuadros pulmonares agudos que obligaron a su hospitalización, en cuyo contexto la paciente (A) presentó una convulsión y la (B) cefalea y compromiso de conciencia, que obligaron a una RM de cerebro. En ambos casos se encontraron múltiples abscesos cerebrales de distinta ubicación y tamaño que no habían dado síntomas focales. La nocardiosis se identificó en la paciente (A) con la biopsia de un micetoma cutáneo y en la (B) con la resolución quirúrgica de un absceso cerebeloso. En ambas se inició tratamiento específico con adecuada respuesta. Sin embargo, las reacciones adversas a la antibioterapia obligaron a suspenderla. Esta suspensión reactivó la infección que complicó y llevó al fallecimiento de las pacientes. Conclusiones: La publicación de varios casos de nocardiosis cerebral parvosintomática en pacientes inmunosuprimidos sugiere que para las infecciones cerebrales por Nocardia la pérdida de la inmunidad celular resulta muy significativa, porque permitiría el ingreso y proliferación de la bacteria al interior del SNC sin generar respuestas clínicas inmediatas. La aparición de síntomas se relacionaría con una tardía alteración de la barrera hematoencefálica, más que con el lento proceso lesional de la Nocardia. Lo que condicionaría su diagnóstico oportuno.
Background: Nocardiosis is caused by several strains of Nocardia, Gram-positive bacteria that infects humans and animals likewise. They develop a systemic infection of pulmonary or cutaneous origin that can spread to the Central Nervous System. It frequently affects immunosupresed patients, in which parvosymptomatic cerebral abscess has been described, visible in magnetic resonance imaging but without focal symptoms. Patients and Methods: We want to communicate two women with renal transplant in immunosupresor treatment who were admitted to our hospital for acute pulmonar disease, during which patient A presented a convulsive episode and patient B headache and stupor, after which CT and MR were obtained. In both cases multiple cerebral abscesses were found, of different sizes and location, with no clinical manifestations. Nocardia diagnosis was made in patient A by biopsy from a cutaneous mycetoma and in patient B after surgery of a cerebellar abscess. In both cases antimicrobial treatment was initiated with good response, but had to be interrupted due to adverse effects. This reactivated the infection, which had a complicated course and finally lead to the death of both patients. Conclusions: The fact that several cases of parvosymtomatic cerebral Nocardiosis in immunosupresed patients have been published suggest that cellular immunosupresion is key in the development of cerebral infections by Nocardia. It probably allows the access and multiplication of the bacteria inside the encephalon without an immediate clinical response. The development of symptoms is probably related to a late alteration of the blood-brain barrier rather than to the slow progression of Nocardia disease.