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1.
Ecol Appl ; 34(2): e2945, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286682

RESUMO

Eutrophication and brownification are ongoing environmental problems affecting aquatic ecosystems. Due to anthropogenic changes, increasing amounts of organic and inorganic compounds are entering aquatic systems from surrounding catchment areas, increasing both nutrients, total organic carbon (TOC), and water color with societal, as well as ecological consequences. Several studies have focused on the ability of wetlands to reduce nutrients, whereas data on their potential to reduce TOC and water color are scarce. Here we evaluate wetlands as a potential multifunctional tool for mitigating both eutrophication and brownification. Therefore, we performed a study for 18 months in nine wetlands allowing us to estimate the reduction in concentrations of total nitrogen (TN), total phosphorus (TP), TOC and water color. We show that wetland reduction efficiency with respect to these variables was generally higher during summer, but many of the wetlands were also efficient during winter. We also show that some, but not all, wetlands have the potential to reduce TOC, water color and nutrients simultaneously. However, the generalist wetlands that reduced all four parameters were less efficient in reducing each of them than the specialist wetlands that only reduced one or two parameters. In a broader context, generalist wetlands have the potential to function as multifunctional tools to mitigate both eutrophication and brownification of aquatic systems. However, further research is needed to assess the design of the generalist wetlands and to investigate the potential of using several specialist wetlands in the same catchment.


Assuntos
Ecossistema , Áreas Alagadas , Eutrofização , Nitrogênio , Água
2.
Semin Cell Dev Biol ; 94: 66-73, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630032

RESUMO

Precise intracellular calcium signaling is crucial to numerous cellular functions. In non-excitable cells, store-operated calcium entry (SOCE) is a key step in the generation of intracellular calcium signals. Tight regulation of SOCE is important, and dysregulation is involved in several pathophysiological cellular malfunctions. The current underlying SOCE, calcium release-activated calcium current (ICRAC), was first discovered almost three decades ago. Since its discovery, the molecular components of ICRAC, Orai1 and stromal interaction molecule 1 (STIM1), have been extensively investigated. Several regulatory mechanisms and proteins contribute to alterations in SOCE and cellular malfunctions in cancer, immune and neurodegenerative diseases, inflammation, and neuronal disorders. This review summarizes these regulatory mechanisms, including glycosylation, pH sensing, and the regulatory proteins golli, α-SNAP, SARAF, ORMDL3, CRACR2A, and TRPM4 channels.


Assuntos
Cálcio/metabolismo , Inflamação/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Doenças Neurodegenerativas/metabolismo , Proteína ORAI1/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Animais , Sinalização do Cálcio , Humanos , Inflamação/patologia , Neoplasias/patologia , Doenças Neurodegenerativas/patologia
3.
Acta Paediatr ; 109(10): 2099-2104, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32017246

RESUMO

AIM: Our previous randomised controlled trial of children with obstructive sleep apnoea (OSA) showed no significant differences between adenotonsillectomy (ATE) and adenotonsillotomy (ATT) in improving nocturnal respiration and quality of life after 1 year. The aim of this report was to evaluate the effects on behavioural symptoms using the Strengths and Difficulties Questionnaire (SDQ). METHODS: Children between 2 and 6 years with OSA were randomised to ATT or ATE. Parents, blinded to method, answered the SDQ while their child underwent polysomnography before and 1 year after surgery. Differences between the total SDQ scores were analysed between the treatment groups. RESULTS: The SDQ was filled out in 87% of the cases preoperatively, and in 86% postoperatively. At follow-up, the mean total SDQ score was 9.6 SD ± 5.1 in the ATE group (n = 31), and 8.2 ± 6.7 in the ATT group (n = 37), P = .09. The mean total SDQ score for all was preoperatively 10.6 ± 5.0, and postoperatively 8.8 ± 6.0, P = .0002. CONCLUSION: There were no significant differences in SDQ scores between the groups at follow-up, indicating that the more conservative ATT is a treatment option in paediatric OSA. The whole group of patients showed a significant improvement after surgery.


Assuntos
Apneia Obstrutiva do Sono , Tonsilectomia , Adenoidectomia , Sintomas Comportamentais , Criança , Humanos , Qualidade de Vida , Apneia Obstrutiva do Sono/cirurgia , Inquéritos e Questionários
4.
Eur Arch Otorhinolaryngol ; 277(10): 2821-2827, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32417961

RESUMO

PURPOSE: In our previous randomized controlled trial (RCT), comparing adenotonsillectomy (ATE) with adenopharyngoplasty (APP) in children with severe obstructive sleep apnea (OSA), there were no differences in respiratory sleep parameters or quality of life. The purpose of the present report was to evaluate postoperative morbidity from this RCT. METHODS: The study was a blinded RCT in 83 children (ATE = 47; APP = 36), 2-4 years of age, with an obstructive apnea-hypopnea index of ≥ 10. Pain was assessed from the first until the tenth day after surgery with a logbook that reported pain by child (FPS-R, Faces Pain Scale-Revised) and caregiver (visual analogue scale), analgesic use, return to normal diet, and weight change. Bleeding, infection, satisfaction with treatment, speech, and swallowing were assessed with a questionnaire and medical records 6 months after surgery. RESULTS: Sixty-four children (77%) returned the logbook and 65 (78%) answered the questionnaire. The median (interquartile range) day the children graded themselves as pain free (FPS-R = 0) was 7 (6-10) after ATE, compared with 9 (7 to > 10) after APP (p = 0.018). There were no other significant differences between the groups regarding any other pain-related outcomes, bleeding, infection, satisfaction, swallowing, or speech, but three children (11%) reported impaired speech after APP compared to none after ATE (p = 0.067). CONCLUSION: The results regarding postoperative morbidity were in favor of ATE and the results from our previous report showed no advantages of APP. Therefore, APP should not be recommended in young, otherwise healthy children with OSA.


Assuntos
Apneia Obstrutiva do Sono , Tonsilectomia , Adenoidectomia , Criança , Pré-Escolar , Humanos , Morbidade , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia/efeitos adversos , Resultado do Tratamento
5.
Int J Mol Sci ; 21(5)2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32182937

RESUMO

Cancers of the digestive tract are among the most prevalent types of cancer. These types of cancers are often diagnosed at a late stage, which results in a poor prognosis. Currently, many biomedical studies focus on the role of ion channels, in particular transient receptor potential (TRP) channels, in cancer pathophysiology. TRP channels show mostly non-selective permeability to monovalent and divalent cations. TRP channels are often dysregulated in digestive tract cancers, which can result in alterations of cancer hallmark functions, such as enhanced proliferation, migration, invasion and the inability to induce apoptosis. Therefore, TRP channels could serve as potential diagnostic biomarkers. Moreover, TRP channels are mostly expressed on the cell surface and ion channel targeting drugs do not need to enter the cell, making them attractive candidate drug targets. In this review, we summarize the current knowledge about TRP channels in connection to digestive tract cancers (oral cancer, esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer) and give an outlook on the potential of TRP channels as cancer biomarkers or therapeutic targets.


Assuntos
Neoplasias Gastrointestinais/metabolismo , Trato Gastrointestinal/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo , Animais , Humanos
6.
Eur Arch Otorhinolaryngol ; 276(11): 3231-3238, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31377901

RESUMO

PURPOSE: Our previous randomized controlled trial (RCT) of children with obstructive sleep apnea (OSA) showed no significant differences between adenotonsillectomy (ATE) and adenotonsillomy (ATE) in improving nocturnal respiration and symptoms after one year. This is the continuous report with the evaluation of postoperative morbidity concerning bleeding and pain. METHODS: A double-blinded RCT including 79 children, aged 2-6 years, with moderate to severe OSA, randomized to either ATE (n = 40) or ATT (n = 39). From one to ten days postoperatively, parents filled in a logbook with six pain-related outcomes (parent and child grading pain at different levels, days of analgesic use and return to normal diet). Peri- and postoperative bleeding were also registered. RESULTS: 63 patients (80%) returned the logbook. There were significant differences between groups in only two of the six pain-related outcomes in favor of the ATT group; first day when the children graded themselves as pain free (p = 0.021, Log Rank Test), and first day the caregiver estimated pain VAS ≤ 5 (p = 0.007, Log Rank Test). Two (5%) cases of postoperative bleeding occurred in the ATE group, one of which needed a return to theatre. No case of postoperative bleeding was seen in the ATT group. CONCLUSIONS: The results from this RCT are in line with previous comparative studies between ATT and ATE. Children operated with ATT had significantly less postoperative pain in one-third of the outcomes, and less bleeding than ATE. However, as the differences in morbidity between the surgical methods were minor the clinical significance is uncertain. TRIAL REGISTRATION: This study was approved by the Swedish Regional Ethics Board in Stockholm, Sweden (Dnr 2011/925-32 and 2013/2274-32) and registered at ClinicalTrials.gov (Trial registration number NCT01676181).


Assuntos
Acetaminofen/administração & dosagem , Adenoidectomia , Dor Pós-Operatória , Hemorragia Pós-Operatória , Tonsilectomia , Adenoidectomia/efeitos adversos , Adenoidectomia/métodos , Analgésicos não Narcóticos/administração & dosagem , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/etiologia , Apneia Obstrutiva do Sono/fisiopatologia , Tonsilectomia/efeitos adversos , Tonsilectomia/métodos , Resultado do Tratamento
7.
BMC Vet Res ; 13(1): 42, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28173799

RESUMO

BACKGROUND: A multiplex qPCR targeting a 128 bp region on the 23S rDNA gene was developed for detection of Brachyspira (B.) hyodysenteriae and B. pilosicoli, the agents of swine dysentery (SD) and porcine intestinal spirochaetosis (PIS), together with a triplet of apathogenic Brachyspira spp. (B. innocens, B. intermedia, B. murdochii) in porcine feces. The multiplex qPCR was evaluated against a duplex PCR (La et al., J Clin Microbiol 41:3372-5, 2003). RESULTS: Using DNA extracted from fecal culture, the multiplex qPCR showed excellent agreement with the duplex PCR (κ = 0.943 and 0.933). In addition, thanks to the three probes whereof one detecting the apathogenic Brachyspria spp., a more diversified overview of the brachyspiral flora in porcine fecal samples can be delivered as a part of the routine diagnostic. The multiplex qPCR with a limit of detection of 5-10 genomic equivalents (GE) per reaction (6 × 102 GE per gram) allows reliable detection of Brachyspira species directly from fecal swab DNA. In line with this, analysis of 202 fecal swabs in comparison with culture-based qPCR showed a high agreement for the causative agents of SD (B.hyodysenteriae: κ = 0.853, sensitivity 87% specificity 98%). CONCLUSION: The novel multiplex qPCR is robust and has a high analytical sensitivity and is therefore suitable for high-throughput screening of porcine fecal swabs for the causative agents of SD. This assay can therefore be used for the direct proof of the pathogenic B. spp. in fecal swabs within the scope of a monitoring program.


Assuntos
Brachyspira/genética , Infecções por Bactérias Gram-Negativas/veterinária , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/microbiologia , Animais , Brachyspira/isolamento & purificação , Fezes/microbiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/microbiologia , Limite de Detecção , Reação em Cadeia da Polimerase/veterinária , RNA Ribossômico 23S/genética , Reprodutibilidade dos Testes , Suínos
8.
Lakartidningen ; 1202023 10 05.
Artigo em Sueco | MEDLINE | ID: mdl-37818820

RESUMO

Obstructive sleep disordered breathing (OSDB) is a spectrum from habitual snoring and labored breathing to obstructive sleep apnea (OSA), which is common and potentially serious in children. The process contains a new question at child care centers, directed at caretakers with children at age 18 months and 3 years, concerning habitual snoring (3 times a week or more). A primary care doctor verifies the suspicion of OSDB in case of a positive answer to one of 7 additional questions or 4 status findings (e.g. tonsil hypertrophy). The process starts with the suspicion of OSDB, from the age of 18 months to 18 years, and ends when symptoms are improved after watchful waiting or upper airway surgery. National equality is a goal, with increased access to nocturnal respiratory recordings of children with comorbidities or doubtful cases. Also, with short waiting time to first visit at ORL department, and to surgery. Children with comorbidities or severe symptoms get postoperative follow-ups with a nurse after 6 months. The new ICD code for OSDB is R06.8A.


Assuntos
Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Tonsilectomia , Criança , Humanos , Lactente , Ronco/cirurgia , Suécia , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/cirurgia , Síndromes da Apneia do Sono/cirurgia
9.
Sleep Med X ; 4: 100055, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36124223

RESUMO

Objectives: Adenotonsillectomy (ATE) is a common treatment for pediatric obstructive sleep apnea (OSA). Intracapsular adenotonsillotomy (ATT) is associated with less postoperative morbidity. Our previous randomized controlled trial (RCT) compared ATE and ATT in otherwise healthy children with moderate to severe OSA. No differences in polysomnographic (PSG) and OSA-18 were found between the groups at one-year follow-up. This study presents the long-term results of the RCT. Methods: Non-obese children (n = 79, 2-6 years) who had undergone either ATE (n = 40) or ATT (n = 39) were offered PSG and OSA-18 questionnaire five-years after surgery. Primary outcome was the group difference in postoperative Obstructive Apnea/Hypopnea Index (OAHI). ATE was recommended to the ATT group if they had a relapse of OSA. Results: The follow-up was completed by 45 of 79 (57%) children; 28 (35%) drop-outs, and six of 39(15%) in the ATT group were excluded after ATE. After ATE(n = 17), OAHI decreased from mean 12.3(SD 8.0) to 0.6(0.7), and after ATT(n = 28) from 12.6(7.4) to 0.5(0.6), a mean difference in postoperative OAHI of 0.1(95% CI -0.3 - 0.5). Sensitivity analyses did not change the results. The median OSA-18 decreased in the ATE group from 57(interquartile range 47-79) to 27(22-36), and in the ATT group from 67(53-79) to 32(25-44), without group differences for postoperative values. Conclusion: The results of this five-year follow-up of otherwise healthy OSA-children showed a high drop-out rate, but indicates that ATT could be an effective treatment for pediatric OSA. However, ATT warrants follow-up due to the risk of recurrence, and further studies are needed.

10.
Laryngoscope Investig Otolaryngol ; 7(6): 2161-2170, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36544930

RESUMO

Objectives: To investigate whether the OSA-18 questionnaire and a postoperative patient-reported outcome measure (PROM) question correlated with polysomnography (PSG) data. Methods: A prospective study of otherwise healthy young children with moderate to severe obstructive sleep apnea (OSA) to investigate if the obstructive apnea-hypopnea index (OAHI) before and 6-12 months after adenotonsil surgery correlated with the OSA-18 total symptom score (TSS) and the sleep disturbance subscale (SDS), as well as a PROM question on symptom improvement with responses on a 4-grade Likert scale. Results: Of 201 children, 173 (86%) had complete data of OAHI and OSA-18 pre- and postoperatively. The mean age was 3.2 years (SD 1.0) and the mean OAHI was 15.9 (11.3). Significant correlations between changes in the OAHI and OSA-18 were found, both TSS (r = 0.29, p < .001) and SDS (r = 0.53, p < .001). A total of 136 (68%) patients responded to the PROM question, the majority of whose symptoms had disappeared (n = 102) or almost disappeared (n = 30). Four patients had unchanged symptoms, and none had worsening symptoms. A correlation was found between the PROM question and a change in the OAHI (r = 0.36, p < .001), as well as a change in the OSA-18 TSS (r = 0.24, p = .006) and the SDS (r = 0.34, p < .001). The specificity of the PROM question for prediction of a postoperative OAHI < 2 was 82%, and the sensitivity was 38%. Conclusion: Changes in the OAHI significantly correlated with changes in the OSA-18, especially with the sleep disturbance scale, which could be an alternative for evaluation at follow-ups. Level of Evidence: 3.

11.
Biomolecules ; 11(2)2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33562811

RESUMO

Transient receptor potential melastatin 4 (TRPM4) is widely expressed in various organs and associated with cardiovascular and immune diseases. Lately, the interest in studies on TRPM4 in cancer has increased. Thus far, TRPM4 has been investigated in diffuse large B-cell lymphoma, prostate, colorectal, liver, breast, urinary bladder, cervical, and endometrial cancer. In several types of cancer TRPM4 is overexpressed and contributes to cancer hallmark functions such as increased proliferation and migration and cell cycle shift. Hence, TRPM4 is a potential prognostic cancer marker and a promising anticancer drug target candidate. Currently, the underlying mechanism by which TRPM4 contributes to cancer hallmark functions is under investigation. TRPM4 is a Ca2+-activated monovalent cation channel, and its ion conductivity can decrease intracellular Ca2+ signaling. Furthermore, TRPM4 can interact with different partner proteins. However, the lack of potent and specific TRPM4 inhibitors has delayed the investigations of TRPM4. In this review, we summarize the potential mechanisms of action and discuss new small molecule TRPM4 inhibitors, as well as the TRPM4 antibody, M4P. Additionally, we provide an overview of TRPM4 in human cancer and discuss TRPM4 as a diagnostic marker and anticancer drug target.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Antineoplásicos/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/uso terapêutico , Canais de Cátion TRPM/genética , Anticorpos Neutralizantes/biossíntese , Antineoplásicos/síntese química , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Transporte de Íons/efeitos dos fármacos , Terapia de Alvo Molecular , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Bibliotecas de Moléculas Pequenas/síntese química , Canais de Cátion TRPM/antagonistas & inibidores , Canais de Cátion TRPM/metabolismo
12.
Cancers (Basel) ; 13(21)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34771564

RESUMO

(1) Background: Transient receptor potential melastatin (TRPM4) ion channel aberrant expression or malfunction contributes to different types of cancer, including colorectal cancer (CRC). However, TRPM4 still needs to be validated as a potential target in anti-cancer therapy. Currently, the lack of potent and selective TRPM4 inhibitors limits further studies on TRPM4 in cancer disease models. In this study, we validated novel TRPM4 inhibitors, CBA, NBA, and LBA, in CRC cells. (2) Methods: The potency to inhibit TRPM4 conductivity in CRC cells was assessed with the whole-cell patch clamp technique. Furthermore, the impact of TRPM4 inhibitors on cellular functions, such as viability, proliferation, and cell cycle, were assessed in cellular assays. (3) Results: We show that in CRC cells, novel TRPM4 inhibitors irreversibly block TRPM4 currents in a low micromolar range. NBA decreases proliferation and alters the cell cycle in HCT116 cells. Furthermore, NBA reduces the viability of the Colo205 cell line, which highly expresses TRPM4. (4) Conclusions: NBA is a promising new TRPM4 inhibitor candidate, which could be used to study the role of TRPM4 in cancer disease models and other diseases.

13.
J Mol Biol ; 433(17): 166665, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-33058873

RESUMO

Transient receptor potential melastatin 4 (TRPM4) is a broadly expressed Ca2+ activated monovalent cation channel that contributes to the pathophysiology of several diseases. For this study, we generated stable CRISPR/Cas9 TRPM4 knockout (K.O.) cells from the human prostate cancer cell line DU145 and analyzed the cells for changes in cancer hallmark functions. Both TRPM4-K.O. clones demonstrated lower proliferation and viability compared to the parental cells. Migration was also impaired in the TRPM4-K.O. cells. Additionally, analysis of 210 prostate cancer patient tissues demonstrates a positive association between TRPM4 protein expression and local/metastatic progression. Moreover, a decreased adhesion rate was detected in the two K.O. clones compared to DU145 cells. Next, we tested three novel TRPM4 inhibitors with whole-cell patch clamp technique for their potential to block TRPM4 currents. CBA, NBA and LBA partially inhibited TRPM4 currents in DU145 cells. However, none of these inhibitors demonstrated any TRPM4-specific effect in the cellular assays. To evaluate if the observed effect of TRPM4 K.O. on migration, viability, and cell cycle is linked to TRPM4 ion conductivity, we transfected TRPM4-K.O. cells with either TRPM4 wild-type or a dominant-negative mutant, non-permeable to Na+. Our data showed a partial rescue of the viability of cells expressing functional TRPM4, while the pore mutant was not able to rescue this phenotype. For cell cycle distribution, TRPM4 ion conductivity was not essential since TRPM4 wild-type and the pore mutant rescued the phenotype. In conclusion, TRPM4 contributes to viability, migration, cell cycle shift, and adhesion; however, blocking TRPM4 ion conductivity is insufficient to prevent its role in cancer hallmark functions in prostate cancer cells.


Assuntos
Neoplasias da Próstata/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/farmacologia , Canais de Cátion TRPM/antagonistas & inibidores , Cálcio/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Masculino , Técnicas de Patch-Clamp/métodos , Neoplasias da Próstata/metabolismo
14.
Am J Obstet Gynecol ; 201(2): 139.e1-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19398092

RESUMO

OBJECTIVE: The aim of this study was to investigate which add-back hormone replacement therapy would be most beneficial in terms of mood effects for patients with premenstrual dysphoric disorder who are receiving gonadotropin-releasing hormone agonist therapy. STUDY DESIGN: Three different add-back hormone replacement treatments were evaluated in a randomized, double-blinded, cross-over clinical trial in 27 patients premenstrual dysphoric disorder. The add-back treatments consisted of 1.5 mg estradiol and 400 mg progesterone, 1.5 mg estradiol and placebo, and 0.5 mg estradiol and 400 mg progesterone. The primary outcome measure was daily symptom ratings for mood and physical symptoms. RESULTS: The highest dose of estradiol in combination with progesterone was associated with the most pronounced symptom recurrence, both in comparison with a lower dose of estradiol together with progesterone and estradiol-only treatment. CONCLUSION: Based on the findings of the present study, long-cycle add-back treatment to avoid frequent progestagen use appears to be most beneficial for patients with premenstrual dysphoric disorder.


Assuntos
Estradiol/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Leuprolida/administração & dosagem , Transtornos do Humor/tratamento farmacológico , Síndrome Pré-Menstrual/tratamento farmacológico , Progesterona/administração & dosagem , Adulto , Afeto/efeitos dos fármacos , Ansiedade/tratamento farmacológico , Estudos Cross-Over , Depressão/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Estradiol/efeitos adversos , Feminino , Humanos , Humor Irritável/efeitos dos fármacos , Leuprolida/efeitos adversos , Pessoa de Meia-Idade , Placebos , Progesterona/efeitos adversos , Resultado do Tratamento
15.
Gynecol Obstet Invest ; 67(1): 49-52, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18843184

RESUMO

BACKGROUND/AIMS: The aim of the study was to assess the prevalence of persisting symptoms 6 months or more after eclampsia. METHODS: During a 2-year period (mid-1998 to mid-2000), 210 patients with eclampsia were included in a prospective cohort study of eclampsia in Denmark, Norway and Sweden. One hundred and twenty-three women (59%) were followed up with a structured telephone interview, 6-24 months (median 11) after their eclamptic fit. RESULTS: At the time of follow-up, 63 women (51%) had at least one persistent symptom; 2 patients had severe neurological sequels (hemiparesis and dysarthria), 11% had visual disturbances, 22% had problems concentrating or recalling phone numbers and messages, 18% reported frequent headaches and 10% had vertigo or balance problems. CONCLUSION: Although few women suffered from severe sequels, many women had persisting symptoms following eclampsia indicating a need for follow-up of these patients. A case-control study comparing the health and symptoms between women having suffered from eclampsia and women without this complication may therefore be justified.


Assuntos
Eclampsia/patologia , Adolescente , Adulto , Estudos de Coortes , Eclampsia/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Entrevistas como Assunto , Gravidez , Estudos Prospectivos , Países Escandinavos e Nórdicos/epidemiologia , Adulto Jovem
16.
Mol Oncol ; 13(11): 2393-2405, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31441200

RESUMO

Transient receptor potential melastatin-4 channel (TRPM4) dysregulation contributes to heart conditions, immune diseases, and cervical and prostate cancer. Up to now, the involvement of TRPM4 in colorectal cancer (CRC) pathophysiology remains unknown. Here, we investigated tumor tissue microarrays from 379 CRC patients and analyzed TRPM4 protein expression, tumor characteristics, and clinical outcome. High TRPM4 protein expression was associated with unfavorable tumor features characteristic for epithelial-mesenchymal transition and infiltrative growth patterns, that is, a high number of tumor buds and a low percentage in tumor border configuration. Compared to CRC cells representing early cancer stages, TRPM4 protein expression was the highest in cells representing late-stage metastatic cancer. Investigation of CRC cell line HCT116 and five CRISPR/cas9 TRPM4 knockout clones demonstrated that TRPM4 exhibited large Na+ current densities (~ 60 pA/pF). In addition, CRISPR/cas9 TRPM4 knockout clones showed a tendency toward decreased migration and invasion, cell viability, and proliferation and exhibited a shift in cell cycle when compared to HCT116. Stable overexpression of TRPM4 (TRPM4 wild-type) in two CRISPR/cas9 TRPM4 knockout clones rescued the decrease in cell viability and cell cycle shift. Stable overexpression of a nonconducting, dominant-negative TRPM4 mutant (TRPM4 D894A) did not rescue the decrease in viability or cell cycle shift. Taken together, these findings pointed to TRPM4 ion channel conductivity as the underlying mechanism for decreased viability and cell cycle shift in the TRPM4 knockout clones. Together with previous findings, our present data suggest that TRPM4 plays a versatile role in cancer cell proliferation, cell cycle, and invasion.


Assuntos
Ciclo Celular , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Canais de Cátion TRPM/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Ativação do Canal Iônico , Invasividade Neoplásica
17.
Psychoneuroendocrinology ; 33(4): 487-96, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18329179

RESUMO

BACKGROUND: Negative mood symptoms remain one of the major reasons for discontinuation of oral contraceptive pills. The aim of this study was to compare acoustic startle response and prepulse inhibition (PPI) in women with different experience of oral contraceptive pills. METHODS: Thirty women currently on combined oral contraceptives (COCs) with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects from treatment, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 32 women who had discontinued COC use due to adverse mood effects were included. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of musculus Orbicularis Oculi. Twenty pulse-alone trials (115dB 40ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115dB 40ms noise burst preceded at a 100ms interval by 20ms prepulses that were 72, 74, 78, or 86dB. RESULTS: Patients with adverse mood effects of COCs exhibited lower levels of PPI with 86dB prepulse compared to COC users with no adverse effects of COCs (p<0.05). There was no difference in PPI between the two groups of prior COC users. No significant difference was found between the groups regarding acoustic startle response. CONCLUSION: Relative to COC users with no reports of adverse mood symptoms, subjects suffering from COC-induced negative mood displayed deficits in PPI of acoustic startle. The fact that there was no difference in PPI between the two groups of prior COC users indicates that deficient PPI is related to adverse mood effects caused by COCs.


Assuntos
Sintomas Afetivos/induzido quimicamente , Piscadela/fisiologia , Anticoncepcionais Orais Combinados/efeitos adversos , Inibição Psicológica , Reflexo de Sobressalto/fisiologia , Estimulação Acústica , Adulto , Piscadela/efeitos dos fármacos , Estudos de Casos e Controles , Feminino , Humanos , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Valores de Referência , Reflexo de Sobressalto/efeitos dos fármacos , Limiar Sensorial/fisiologia , Estatísticas não Paramétricas
19.
Pediatrics ; 139(4)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28320866

RESUMO

BACKGROUND: Adenotonsillectomy (ATE) is a well-established and effective treatment of pediatric obstructive sleep apnea (OSA). In recent years, a more conservative method, adenotonsillotomy (ATT), has gained popularity because it is associated with less postoperative morbidity. Yet no previous randomized study has compared these 2 methods regarding their effectiveness in treating pediatric OSA in terms of polysomnographic data, which was the primary aim of this study. The hypothesis was that ATT is noninferior to ATE after 1 year. METHODS: Seventy-nine children, aged 2 to 6 years, with OSA (Apnea-Hypopnea Index [AHI] 5-30) were randomized to ATT (n = 40) or ATE (n = 39). Polysomnography (PSG) and questionnaire OSA-18 were assessed at baseline and 1 year postsurgery. RESULTS: Mean difference between groups in the primary outcome, change in AHI, was 0.83, 95% confidence interval -3.2 to 4.9, not exceeding the noninferiority margin of 5. After ATE, AHI decreased from median 12.7 (interquartile range 8.3-19.1) to 2.0 (1.2-3.1) and after ATT from 15.8 (8.5-21.2) to 4.0 (1.2-5.1). For both groups, significant improvements of PSG and OSA-18 questionnaire outcomes were observed, with no significant differences between groups. Five children (13%) in the ATT group needed repeated surgery for tonsil regrowth and recurrence of OSA. CONCLUSIONS: The results suggest that ATT is noninferior to ATE in treating pediatric OSA regarding PSG outcomes after 1 year. ATT could be considered an alternative to ATE for treatment of pediatric OSA. However, after ATT, there is a nonnegligible risk of recurrence of OSA, and this should be taken into account when selecting surgical method.


Assuntos
Adenoidectomia/métodos , Polissonografia/métodos , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia/métodos , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários , Suécia , Resultado do Tratamento
20.
BMJ Open ; 7(1): e013346, 2017 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-28087550

RESUMO

OBJECTIVES: The objective of this study was to longitudinally describe the history of tonsil surgery in Swedish children and adolescents regarding incidence, indications for surgery, surgical methods and the age and gender distributions. SETTING: A retrospective longitudinal population-based cohort study based on register data from the Swedish National Patient Register (NPR) and population data from Statistics Sweden. PARTICIPANTS: All Swedish children 1-<18 years registered in the NPR with a tonsil surgery procedure 1987-2013. RESULTS: 167 894 tonsil surgeries were registered in the NPR 1987-2013. An increase in the total incidence rate was observed, from 22/10 000 person years in 1987 to 47/10 000 in 2013. The most marked increase was noted in children 1-3 years of age, increasing from 17 to 73/10 000 person years over the period. The proportion children with obstructive/sleep disordered breathing (SDB) indications increased from 42.4% in 1987 to 73.6% in 2013. Partial tonsillectomy, tonsillotomy (TT), increased since 1996 and in 2013 55.1% of all tonsil procedures were TTs. CONCLUSIONS: There have been considerable changes in clinical practice for tonsil surgery in Swedish children over the past few decades. Overall, a doubling in the total incidence rate was observed. This increase consisted mainly of an increase in surgical procedures due to obstructive/SDB indications, particularly among the youngest age group (1-3 years old). TT has gradually replaced tonsillectomy as the predominant method for tonsil surgery.


Assuntos
Tonsilectomia/estatística & dados numéricos , Tonsilectomia/tendências , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Tonsila Palatina/cirurgia , Sistema de Registros , Estudos Retrospectivos , Apneia Obstrutiva do Sono/epidemiologia , Suécia/epidemiologia , Tonsilite/epidemiologia
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