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2.
Arq Neuropsiquiatr ; 78(8): 494-500, 2020 08 03.
Article in English | MEDLINE | ID: mdl-32756734

ABSTRACT

BACKGROUND: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. OBJECTIVE: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. METHODS: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. RESULTS: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). CONCLUSIONS: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.


Subject(s)
Coronavirus Infections/diagnosis , Nervous System Diseases/etiology , Pandemics , Pneumonia, Viral/diagnosis , Referral and Consultation/statistics & numerical data , Betacoronavirus , Brazil/epidemiology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Hospital Bed Capacity , Hospitals, University , Humans , Nervous System Diseases/diagnosis , Nervous System Diseases/therapy , Neurology , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Retrospective Studies , SARS-CoV-2
3.
Arq. neuropsiquiatr ; 78(8): 494-500, Aug. 2020. tab, graf
Article in English | LILACS | ID: biblio-1131736

ABSTRACT

ABSTRACT Background: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. Objective: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. Results: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.


RESUMO Introdução: Mais de um terço dos pacientes com COVID-19 apresentam sintomas neurológicos que variam de anosmia a AVC e encefalopatia. Além disso, doenças neurológicas prévias podem exigir tratamento especial e estar associadas a piores desfechos. Não obstante, o papel dos neurologistas na COVID-19 é provavelmente pouco reconhecido. Objetivo: O objetivo deste estudo foi relatar os motivos para solicitar consultas neurológicas por clínicos e intensivistas em um hospital dedicado à COVID-19. Métodos: Estudo retrospectivo realizado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brasil, um centro dedicado à COVID-19 com 900 leitos (incluindo 300 leitos para unidades de terapia intensiva). O diagnóstico de COVID-19 foi confirmado por SARS-CoV-2-RT-PCR em swabs nasais. Todas as interconsultas de neurologia hospitalar entre 23 de março e 23 de maio de 2020 foram analisadas. Os neurologistas realizaram o exame neurológico, avaliaram todos os dados disponíveis para diagnosticar a patologia neurológica e solicitaram exames adicionais conforme necessidade. Diagnósticos difíceis foram estabelecidos em reuniões de consenso. Após o diagnóstico, os neurologistas participaram da condução dos casos. Resultados: Foram solicitadas consultas neurológicas para 89 de 1.208 (7,4%) em pacientes internados por COVID-19 durante o período. Os principais diagnósticos neurológicos incluíram: encefalopatia (44,4%), acidente vascular cerebral (16,7%), doenças neurológicas prévias (9,0%), crises epilépticas (9,0%), transtornos neuromusculares (5,6%), outras lesões encefálicas agudas (3,4%) e outros sintomas leves inespecíficos (11,2%). Conclusões: A maioria das consultas neurológicas em um hospital dedicado à COVID-19 foi solicitada para condições graves que poderiam afetar o desfecho clínico. Os médicos na linha de frente devem ser capazes de reconhecer sintomas neurológicos. Os neurologistas são membros importantes da equipe médica no atendimento hospitalar à COVID-19.


Subject(s)
Humans , Pneumonia, Viral/diagnosis , Referral and Consultation/statistics & numerical data , Coronavirus Infections/diagnosis , Pandemics , Nervous System Diseases/etiology , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Brazil/epidemiology , Retrospective Studies , Coronavirus Infections , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Betacoronavirus , Hospital Bed Capacity , Hospitals, University , Nervous System Diseases/diagnosis , Nervous System Diseases/therapy , Neurology
4.
Preprint in English | SciELO Preprints | ID: pps-971

ABSTRACT

Background: More than one-third of COVID-19 patients present neurological symptomsranging from anosmia to stroke and encephalopathy. Furthermore, pre-existingneurological conditions may require special treatment and may be associated with worseoutcomes. Notwithstanding, the role of neurologists in COVID-19 is probablyunderrecognized. Objective: The aim of this study was to report the reasons forrequesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital dasClínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bedCOVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosiswas confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurologyconsultations between March 23rd and May 23rd, 2020 were analyzed. Neurologistsperformed the neurological exam, assessed all available data to diagnose theneurological condition, and requested additional tests deemed necessary. Difficultdiagnoses were established in consensus meetings. After diagnosis, neurologists wereinvolved in the treatment. Results: Neurological consultations were requested for 89 outof 1,208 (7.4%) inpatient COVID admissions during that period. Main neurologicaldiagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurologicaldiseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brainlesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Mostneurological consultations in a COVID-19-dedicated hospital were requested for severeconditions that could have an impact on the outcome. First-line doctors should be able torecognize neurological symptoms; neurologists are important members of the medicalteam in COVID-19 hospital care.


Introdução: Mais de um terço dos pacientes com COVID-19 apresentam sintomasneurológicos que variam de anosmia a AVC e encefalopatia. Além disso, doençasneurológicas prévias podem exigir tratamento especial e estar associadas a pioresdesfechos. Não obstante, o papel dos neurologistas na COVID-19 é provavelmentepouco reconhecido. Objetivo: O objetivo deste estudo foi relatar os motivos para solicitarconsultas neurológicas por clínicos e intensivistas em um hospital dedicado à COVID-19. Métodos: Estudo retrospectivo realizado no Hospital das Clínicas da Faculdade deMedicina da Universidade de São Paulo, Brasil, um centro dedicado à COVID-19 com900 leitos (incluindo 300 leitos para unidades de terapia intensiva). O diagnóstico deCOVID-19 foi confirmado por SARS-CoV-2-RT-PCR em swabs nasais. Todas asinterconsultas de neurologia hospitalar entre 23 de março e 23 de maio de 2020 foramanalisadas. Os neurologistas realizaram o exame neurológico, avaliaram todos os dadosdisponíveis para diagnosticar a patologia neurológica e solicitaram exames adicionaisconforme necessidade. Diagnósticos difíceis foram estabelecidos em reuniões deconsenso. Após o diagnóstico, os neurologistas participaram da condução dos casos.Resultados: Foram solicitadas consultas neurológicas para 89 de 1.208 (7,4%) empacientes internados por COVID-19 durante o período. Os principais diagnósticosneurológicos incluíram: encefalopatia (44,4%), acidente vascular cerebral (16,7%),doenças neurológicas prévias (9,0%), crises epilépticas (9,0%), transtornosneuromusculares (5,6%), outras lesões encefálicas agudas (3,4%) e outros sintomasleves inespecíficos (11,2%). Conclusões: A maioria das consultas neurológicas em umhospital dedicado à COVID-19 foi solicitada para condições graves que poderiam afetaro desfecho clínico. Os médicos na linha de frente devem ser capazes de reconhecersintomas neurológicos. Os neurologistas são membros importantes da equipe médica noatendimento hospitalar à COVID-19.

5.
Ann Oncol ; 29(12): 2288-2295, 2018 12 01.
Article in English | MEDLINE | ID: mdl-30304498

ABSTRACT

Quality of life (QoL) is a relevant end point and a topic of growing interest by both scientific community and regulatory authorities. Our aim was to review QoL prevalence as an end point in cancer phase III trials published in major journals and to evaluate QoL reporting deficiencies in terms of under-reporting and delay of publication. All issues published between 2012 and 2016 by 11 major journals were hand-searched for primary publications of phase III trials in adult patients with solid tumors. Information about end points was derived from paper and study protocol, when available. Secondary QoL publications were searched in PubMed. In total, 446 publications were eligible. In 210 (47.1%), QoL was not included among end points. QoL was not an end point in 40.1% of trials in the advanced/metastatic setting, 39.7% of profit trials and 53.6% of non-profit trials. Out of 231 primary publications of trials with QoL as secondary or exploratory end point, QoL results were available in 143 (61.9%). QoL results were absent in 37.6% of publications in the advanced/metastatic setting, in 37.1% of profit trials and 39.3% of non-profit trials. Proportion of trials not including QoL as end point or with missing QoL results was relevant in all tumor types and for all treatment types. Overall, 70 secondary QoL publications were found: for trials without QoL results in the primary publication, probability of secondary publication was 12.5%, 30.9% and 40.3% at 1, 2 and 3 years, respectively. Proportion of trials not reporting QoL results was similar in trials with positive results (36.5%) and with negative results (39.4%), but the probability of secondary publication was higher in positive trials. QoL is not included among end points in a relevant proportion of recently published phase III trials in solid tumors. In addition, QoL results are subject to significant under-reporting and delay in publication.


Subject(s)
Clinical Trials, Phase III as Topic/standards , Medical Oncology/standards , Neoplasms/therapy , Quality of Life , Randomized Controlled Trials as Topic/standards , Humans , Neoplasms/mortality , Neoplasms/psychology , Patient Reported Outcome Measures , Practice Guidelines as Topic , Progression-Free Survival , Research Design/standards
6.
Article in English | MEDLINE | ID: mdl-27726223

ABSTRACT

The Multidimensional Geriatric Assessment (MGA) is currently used for assessing geriatric oncological patients, but a new prognostic index - the Multidimensional Prognostic Index (MPI) - has a demonstrated prognostic value in cancer patients too. The present work was designed to compare the MPI and MGA as predictors of 12-month mortality. 160 patients ≥70 years old with locally-advanced or metastatic solid cancers consecutively joining our Geriatric Oncology Program were administered a Comprehensive Geriatric Assessment to calculate their MGA and MPI scores. SETTINGS: Geriatric Clinic, Geriatric Surgery Clinic, Medical Oncology Unit, Padova Hospital, Italy. Using Cohen's Kappa coefficient, there was a poor concordance between the MPI and MGA. Severe MPI being associated with a higher mortality risk than Frail in the MGA. The ROC curves indicated that the MPI had a greater discriminatory power for 12-month mortality than the MGA. In our population of elderly cancer patients, the MPI performed better than the MGA in predicting mortality. Further evidence from larger prospective trials is needed to establish whether other geriatric scales, such as the GDS and CIRS-SI, could enhance the value of prognostic indexes applied to elderly cancer patients.


Subject(s)
Geriatric Assessment/methods , Neoplasms/mortality , Severity of Illness Index , Aged , Aged, 80 and over , Female , Humans , Italy/epidemiology , Male , Prognosis , Prospective Studies , ROC Curve
7.
Neuropathol Appl Neurobiol ; 43(2): 133-153, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27178390

ABSTRACT

AIMS: Cytoplasmic accumulation of the nuclear protein transactive response DNA-binding protein 43 (TDP-43) is an early determinant of motor neuron degeneration in most amyotrophic lateral sclerosis (ALS) cases. We previously disclosed this accumulation in circulating lymphomonocytes (CLM) of ALS patients with mutant TARDBP, the TDP-43-coding gene, as well as of a healthy individual carrying the parental TARDBP mutation. Here, we investigate TDP-43 subcellular localization in CLM and in the constituent cells, lymphocytes and monocytes, of patients with various ALS-linked mutant genes. METHODS: TDP-43 subcellular localization was analysed with western immunoblotting and immunocytofluorescence in CLM of healthy controls (n = 10), patients with mutant TARDBP (n = 4, 1 homozygous), valosin-containing protein (VCP; n = 2), fused in sarcoma/translocated in liposarcoma (FUS; n = 2), Cu/Zn superoxide dismutase 1 (SOD1; n = 6), chromosome 9 open reading frame 72 (C9ORF72; n = 4), without mutations (n = 5) and neurologically unaffected subjects with mutant TARDBP (n = 2). RESULTS: TDP-43 cytoplasmic accumulation was found (P < 0.05 vs. controls) in CLM of patients with mutant TARDBP or VCP, but not FUS, in line with TDP-43 subcellular localization described for motor neurons of corresponding groups. Accumulation also characterized CLM of the healthy individuals with mutant TARDBP and of some patients with mutant SOD1 or C9ORF72. In 5 patients, belonging to categories described to carry TDP-43 mislocalization in motor neurons (3 C9ORF72, 1 TARDBP and 1 without mutations), TDP-43 cytoplasmic accumulation was not detected in CLM or in lymphocytes but was in monocytes. CONCLUSIONS: In ALS forms characterized by TDP-43 mislocalization in motor neurons, monocytes display this alteration, even when not manifest in CLM. Monocytes may be used to support diagnosis, as well as to identify subjects at risk, of ALS and to develop/monitor targeted treatments.


Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Monocytes/metabolism , Adult , Aged , Female , Humans , Male , Middle Aged , Mutation
8.
Transplant Proc ; 47(10): 2799-804, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26707291

ABSTRACT

BACKGROUND: Anonymity has been central to medical, psychosocial, and societal practices in organ donation and transplantation. The purpose of this investigation was to explore transplant professionals' views on anonymity in the context of organ transplantation. METHODS: The study consisted of an electronic 18-item survey distributed to the Canadian Society of Transplantation membership, asking about anonymity vs open communication/contact between organ recipients and donor families. RESULTS: Of the 541 members surveyed, 106 replied. Among respondents, 71% felt that organ recipients and donor families should only communicate anonymously, yet 47% felt that identifying information could be included in correspondence between consenting recipients and donor families. When asked whether organ recipients and donor families should be allowed to meet, 53% of respondents agreed, 27% disagreed, and 20% neither agreed nor disagreed. With social media facilitating communication and eliminating the ability to maintain donor/recipient anonymity, 38% of respondents felt that a reexamination of current policies and practices pertaining to anonymity was necessary. CONCLUSION: In conclusion, there was no dominant position on the issue of anonymity/communication between donor families and transplant recipients. Further research and discussion concerning the views of healthcare professionals, organ recipients, and donor families on the mandate of anonymity is needed and may influence future policy.


Subject(s)
Attitude of Health Personnel , Confidentiality , Tissue Donors , Transplant Recipients , Adult , Canada , Female , Humans , Male , Middle Aged , Societies, Medical , Surveys and Questionnaires , Young Adult
10.
Tech Coloproctol ; 19(6): 333-8, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25744688

ABSTRACT

BACKGROUND: The therapy of pelvic floor dyssynergia is mostly conservative and is based on a high-fiber diet, physical activity and biofeedback training. Our aim was to compare the outcome of biofeedback (manometric-assisted pelvic relaxation and simulated defecation training) plus transanal electrostimulation with standard therapy (diet, exercise, laxatives). METHODS: Clinical, physiologic and quality of life [patient assessment of constipation quality of life (PAC-QOL)] measures, anorectal manometry and balloon expulsion test results were collected prospectively at baseline, at the end of the treatment and 6 months after treatment. Primary outcome was the modification of the Wexner score for defecation (WS) and the obstructed defecation score (ODS). Secondary outcomes were the modifications of anorectal manometry pattern and quality of life after treatment. RESULTS: The mean WS and ODS decreased significantly in the EMG biofeedback group: The WS decreased from 16.7 ± 4 to 10 ± 3.5 p < 0.0102, and the ODS decreased from 18.3 ± 5.5 to 5.7 ± 1.8, p < 0.0001. Besides, WS and ODS did not change significantly in the control group. The PAC-QOL score improved significantly from 61 ± 8.6 to 23 ± 4.8 (p < 0.0001) in the EMG biofeedback group; otherwise, the PAC-QOL score did not change significantly in the control group. CONCLUSIONS: Biofeedback therapy plus transanal electrostimulation provided sustained improvement in bowel symptoms and anorectal function in constipated subjects with dyssynergic defecation, whereas standard therapy was largely ineffective.


Subject(s)
Ataxia/therapy , Biofeedback, Psychology/methods , Electric Stimulation Therapy/methods , Pelvic Floor Disorders/therapy , Adult , Anal Canal/physiopathology , Combined Modality Therapy , Constipation/physiopathology , Constipation/psychology , Defecation/physiology , Humans , Prospective Studies , Quality of Life , Rectum/physiopathology , Severity of Illness Index , Treatment Outcome
11.
Science ; 346(6207): 1255757, 2014 Oct 17.
Article in English | MEDLINE | ID: mdl-25324399

ABSTRACT

The heating of the outer solar atmospheric layers, i.e., the transition region and corona, to high temperatures is a long-standing problem in solar (and stellar) physics. Solutions have been hampered by an incomplete understanding of the magnetically controlled structure of these regions. The high spatial and temporal resolution observations with the Interface Region Imaging Spectrograph (IRIS) at the solar limb reveal a plethora of short, low-lying loops or loop segments at transition-region temperatures that vary rapidly, on the time scales of minutes. We argue that the existence of these loops solves a long-standing observational mystery. At the same time, based on comparison with numerical models, this detection sheds light on a critical piece of the coronal heating puzzle.

12.
Science ; 346(6207): 1255732, 2014 Oct 17.
Article in English | MEDLINE | ID: mdl-25324398

ABSTRACT

The solar chromosphere and transition region (TR) form an interface between the Sun's surface and its hot outer atmosphere. There, most of the nonthermal energy that powers the solar atmosphere is transformed into heat, although the detailed mechanism remains elusive. High-resolution (0.33-arc second) observations with NASA's Interface Region Imaging Spectrograph (IRIS) reveal a chromosphere and TR that are replete with twist or torsional motions on sub-arc second scales, occurring in active regions, quiet Sun regions, and coronal holes alike. We coordinated observations with the Swedish 1-meter Solar Telescope (SST) to quantify these twisting motions and their association with rapid heating to at least TR temperatures. This view of the interface region provides insight into what heats the low solar atmosphere.

13.
Mar Pollut Bull ; 80(1-2): 30-40, 2014 Mar 15.
Article in English | MEDLINE | ID: mdl-24529849

ABSTRACT

The Water Framework Directive uses the "one-out, all-out" principle in assessing water bodies (i.e., the worst status of the elements used in the assessment determines the final status of the water body). In this study, we assessed the ecological status of two coastal lakes in Italy. Indices for all biological quality elements used in transitional waters from the Italian legislation and other European countries were employed and compared. Based on our analyses, the two lakes require restoration, despite the lush harbor seagrass beds, articulated macrobenthic communities and rich fish fauna. The "one-out, all-out" principle tends to inflate Type I errors, i.e., concludes that a water body is below the "good" status even if the water body actually has a "good" status. This may cause additional restoration costs where they are not necessarily needed. The results from this study strongly support the need for alternative approaches to the "one-out, all-out" principle.


Subject(s)
Ecosystem , Environmental Restoration and Remediation/legislation & jurisprudence , Lakes/chemistry , Aquatic Organisms/classification , Aquatic Organisms/growth & development , Biodiversity , Costs and Cost Analysis , Environmental Monitoring/legislation & jurisprudence , Environmental Restoration and Remediation/economics , Environmental Restoration and Remediation/methods , Italy , Risk , Water Pollutants/analysis
15.
Tech Coloproctol ; 16(1): 37-53, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22170252

ABSTRACT

BACKGROUND: Laparoscopic rectopexy to treat full-thickness rectal prolapse has proven short-term benefits, but there are few long-term follow-up and functional outcome data available. Using meta-analysis techniques, this study was designed to evaluate long-term results of open and laparoscopic abdominal procedures to treat full-thickness rectal prolapse in adults. METHODS: A literature review was performed using the National Library of Medicine's PubMed database. All articles on abdominal rectopexy patients with a follow-up longer than 16 months were considered. The primary end point was recurrence of rectal prolapse, and the secondary end points were improvement in incontinence and constipation. A random effect model was used to aggregate the studies reporting these outcomes, and heterogeneity was assessed. RESULTS: Eight comparative studies, consisting of a total of 467 patients (275 open and 192 laparoscopic), were included. Analysis of the data suggested that there is no significant difference in recurrence, incontinence and constipation improvement between laparoscopic abdominal rectopexy and open abdominal rectopexy. Considering non-comparative trials, the event rate for recurrence was similar in open and laparoscopic suture rectopexy studies and in open and laparoscopic mesh rectopexy trials. Improvement in constipation after the intervention was not statistically significant except for open mesh repair; postoperative improvement in incontinence was statistically significant after laparoscopic procedures and open mesh rectopexy. CONCLUSIONS: Laparoscopic abdominal rectopexy is a safe and feasible procedure, which may compare equally with the open technique with regard to recurrence, incontinence and constipation. However, large-scale randomized trials, with comparative, strong methodology, are still needed to identify outcome measures accurately.


Subject(s)
Constipation/physiopathology , Fecal Incontinence/physiopathology , Rectal Prolapse/complications , Rectal Prolapse/surgery , Constipation/etiology , Fecal Incontinence/etiology , Humans , Laparoscopy/adverse effects , Recurrence , Surgical Mesh , Suture Techniques
16.
Oncogene ; 31(5): 624-33, 2012 Feb 02.
Article in English | MEDLINE | ID: mdl-21725361

ABSTRACT

We have recently shown that the adaptor protein p140Cap regulates tumor properties in terms of cell motility and growth. Here, by using the highly metastatic rat adenocarcinoma cell line MTLn3-epidermal growth factor receptor (EGFR), we assess the role of p140Cap in metastasis formation. Orthotopic transplantation of MTLn3-EGFR cells over-expressing p140Cap in Rag2(-/-)γ(c)(-/-) mice resulted in normal primary tumor growth compared with the controls. Strikingly, p140Cap over-expression causes an 80% inhibition in the number of lung metastases. p140Cap over-expressing cells display a 50% reduction in directional cell migration, an increased number and size of focal adhesions, and a strong impairment in the ability to invade in a 3D matrix. p140Cap over-expression affects EGFR signaling and tyrosine phosphorylation of cortactin in response to EGF stimulation. Intriguingly, p140Cap associates with cortactin via interaction with its second proline-rich domain to the cortactin SH3 domain. The phosphomimetic cortactin tyrosine 421 mutant rescues migration and invasive properties in p140Cap over-expressing cells. Taken together, these data demonstrate that p140Cap suppresses the invasive properties of highly metastatic breast carcinoma cells by inhibiting cortactin-dependent cell motility.


Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , Cortactin/metabolism , Mammary Neoplasms, Experimental/metabolism , Adaptor Proteins, Vesicular Transport/genetics , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Animals , Cell Line, Tumor , Cell Movement , Cortactin/genetics , Epidermal Growth Factor/pharmacology , ErbB Receptors/genetics , ErbB Receptors/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , HEK293 Cells , Humans , Immunohistochemistry , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/secondary , Mammary Neoplasms, Experimental/genetics , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Knockout , Microscopy, Fluorescence, Multiphoton , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Transplantation , Phosphorylation/drug effects , Protein Binding , RNA Interference , Rats , Transplantation, Heterologous
17.
Am J Transplant ; 11(3): 619-22, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21342451

ABSTRACT

Transplant recipients are encouraged to write anonymous thank-you letters to the donor family. We prospectively explored heart transplant recipients' embodied responses to the 'obligation' to write a thank-you letter using audio/video-taped open-ended interviews (N = 27). Fifteen of the 19 participants, who wrote letters to the donor family, expressed or visually revealed significant distress about issues such as the obligation to write anonymously and the inadequacy of the 'thank-you'. Writing the thank-you letter is not a neutral experience for heart transplant recipients. Rethinking the obligatory practice regarding the thank-you letter and developing the necessary support for the recipient through this process is necessary.


Subject(s)
Correspondence as Topic , Family/psychology , Heart Transplantation/psychology , Tissue Donors/psychology , Adolescent , Adult , Aged , Communication , Cross-Sectional Studies , Feedback, Psychological , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Young Adult
18.
J Cell Biochem ; 104(6): 2155-64, 2008 Aug 15.
Article in English | MEDLINE | ID: mdl-18449939

ABSTRACT

Sympathetic nervous system (SNS) fibres and alpha- and beta-receptors are present in bone, indicating that the SNS may participate in bone metabolism. The importance of these observations is controversial because stimulation or inhibition of the SNS has had various effects upon both anabolic and catabolic activity in this tissue. In this study we evaluated the effects of pharmacological sympathectomy, using chronic treatment of maturing male rats with 40 mg of guanethidine/kg i.p., upon various parameters in bone. Double labelling with tetracycline injection was also performed 20 and 2 days before sacrifice. Bone mass, mineral content, density and histomorphometric characteristics in different skeletal regions were determined. Bone metabolic markers included urinary deoxypyridinoline and serum osteocalcin measurements. Guanethidine significantly reduced the accretion of lumbar vertebral bone and of mineral content and density, compared to controls. Femoral bone mineral content and density were also significantly reduced, compared to controls. Histomorphometric analyses indicated these effects were related to a reduction of cortical bone and mineral apposition rate at femoral diaphysials level. Both markers of bone metabolism were reduced in controls as they approached maturity. Guanethidine significantly decreased serum osteocalcin compared to controls, while urinary deoxypyridinoline was unchanged. These data indicate that guanethidine-induced sympathectomy caused a negative balance of bone metabolism, leading to decreased mass by regulating deposition rather than resorption during modeling and remodeling of bone.


Subject(s)
Bone Development , Bone and Bones/anatomy & histology , Sympathectomy , Absorptiometry, Photon , Amino Acids/urine , Animals , Biomarkers/metabolism , Body Weight/drug effects , Bone Density/drug effects , Bone Development/drug effects , Bone and Bones/drug effects , Femur/drug effects , Guanethidine/administration & dosage , Guanethidine/toxicity , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/physiology , Male , Osteocalcin/blood , Rats , Rats, Sprague-Dawley
19.
Environ Monit Assess ; 140(1-3): 191-209, 2008 May.
Article in English | MEDLINE | ID: mdl-17671848

ABSTRACT

In order to evaluate the impact of atmospheric pollutants emitted by the industrial settlement of Milazzo (Italy) on agriculture, sulphur dioxide and ozone levels in air were monitored and the data were used to estimate yield losses of the most widespread cultures. Trace element concentrations in crops and soils were also detected and metabolic profiles of soil microbial communities were considered. Vibrio fischeri test was used to appraise airborne pollutant ecotoxicity and epidemiological studies on causes of death distribution were carried out to characterize health state of people living in the area. All the sampling points were selected in farms on the basis of a theoretical meteo-diffusive model of industrial air pollutants. Experimental SO2 and O3 values mainly exceeded the threshold established by Italian and EU regulations to protect vegetation and they correspond to estimated significant crop losses. Conversely toxic element residues in soils and in agroalimentary products were generally lower than the fixed values. SO2 and O3 concentrations, toxic element contents and ecotoxicity levels of airborne pollutants were not related only to industrial site emissions, while the fluctuations on metabolic profiles of soil microbial communities seem to agree with the predicted deposition of xenobiotic compounds from the industrial plants. The epidemiological study evidenced a better health state of populations living in the investigated area than in the Messina province and the Sicily region but, inside the area, males living in the municipalities closest to the industrial settlement exhibited a worst health state than those in the very far ones.


Subject(s)
Agriculture , Air Pollution , Ecosystem , Urban Health , Cause of Death , Female , Humans , Italy , Male , Ozone/analysis , Soil Microbiology , Soil Pollutants/analysis , Sulfur Dioxide/analysis , Vegetables/chemistry
20.
Lett Appl Microbiol ; 41(6): 464-9, 2005.
Article in English | MEDLINE | ID: mdl-16305671

ABSTRACT

AIMS: To determine the effectiveness of a packaging film coated with nisin to inhibit Micrococcus luteus ATCC 10240 in tryptone soya broth (TSB) and the microbiota of raw milk during storage. A further aim was to examine the release of nisin from the activated film. METHODS AND RESULTS: An active package, obtained from nisin-treated film, was filled with 1 l of M. luteus ATCC 10240 (ML) suspension in TSB and stored at 4 and 25 degrees C for 2 days. After 24 h at 25 degrees C there was a remarkable reduction of M. luteus ATCC 10240 compared with the control, while at 4 degrees C a slight reduction was observed. Moreover, microbial growth was controlled when 1 l of three different kinds of milk was poured into the active package and stored at 4 degrees C for 7 days. The most significant results were observed in raw milk and pasteurized milk with a reduction of 0.9 log and 1.3 log, respectively. The release experiments showed that nisin release from the film was unpredictable, but it was favoured by low pH and high temperature. CONCLUSIONS: It appears that nisin-coated films were effective in inhibiting M. luteus ATCC 10240 in TSB and the bacterial flora in milk, and the release of nisin was pH and temperature dependent. SIGNIFICANCE AND IMPACT OF THE STUDY: Nisin-activated film may control bacterial growth, maintaining food quality, safety and extending the shelf-life of food products.


Subject(s)
Anti-Bacterial Agents/pharmacology , Food Packaging/methods , Food Preservation/methods , Micrococcus luteus/drug effects , Nisin/pharmacology , Animals , Food Microbiology , Micrococcus luteus/growth & development , Milk/microbiology
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