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1.
J Endocrinol Invest ; 47(4): 937-946, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37819412

ABSTRACT

PURPOSE: Current smoking is a risk factor for osteoporosis (Op), but few data are available regarding the passive smoke impact on Op susceptibility. This cross-sectional study aimed to evaluate the association between the smoking habits and Op in community-dwelling women undergoing dual-energy X-ray absorptiometry (DXA). METHODS: On 01/06/2018, general practitioners from "COMEGEN" Medical Cooperative, Naples, Italy, selected the medical records from the last 10 years of women who had a measurement of bone mineral density performed and simultaneously completed a questionnaire about their smoking behaviour and their cohabiters'. The binary logistic regression analysis was used to estimate the role of passive smoke on the risk of Op, adjusting for age and body mass index (BMI). RESULTS: Among 10,616 subjects, 3942 were currently smokers [CS; mean age 69.4 ± 10.4 years; BMI 27.0 ± 4.9 kg/m2], 873 were passive smokers (PS; mean age 67.8 ± 11.6 years; BMI 27.0 ± 4.9 kg/m2) and 5781 were never smokers (NS; mean age 67.8 ± 11.6 years; body mass index (BMI) 27.0 ± 4.9 kg/m2). Of all, 8562 women (mean age 70.3 ± 10.2 yrs; BMI 27.0 ± 4.9 kg/m2) received the Op diagnosis. PS showed an increased Op risk compared to NS [odds ratio (OR) 1.38 (1.14-1.67)] and comparable to CS [OR 1.02 (0.84-1.24)]. CONCLUSION: The study results demonstrate an association between passive smoke and Op in community-dwelling women already presenting with susceptibility to Op according to Italian essential assistance levels, suggesting that passive and active smoke are equivalent Op risk factors in women.


Subject(s)
Osteoporosis , Tobacco Smoke Pollution , Female , Humans , Middle Aged , Aged , Aged, 80 and over , Absorptiometry, Photon/methods , Tobacco Smoke Pollution/adverse effects , Cross-Sectional Studies , Osteoporosis/chemically induced , Bone Density , Risk Factors
2.
J Endocrinol Invest ; 45(2): 309-315, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34313972

ABSTRACT

PURPOSE: We have recently demonstrated a significant association between osteoporosis (Op) and metabolic syndrome (MetS) in Caucasian women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. This cross-sectional study was performed to evaluate the association between MetS and Op in Caucasian men enrolled in the same geographical area, with identical criteria and in the same time range. METHODS: Among subjects enrolled in the SIMON study, we selected the medical records of all free-living men who performed a contextual evaluation of both bone mineral density (BMD) by DXA and MetS constitutive elements (arterial blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose). All enrolled subjects refer to "COMEGEN" general practitioners' cooperative operating in Naples, Southern Italy. RESULTS: Overall, the medical records of 880 men were examined. No significant association between MetS and Op was observed. Among MetS constitutive elements, waist circumference was inversely related to Op risk. CONCLUSION: In Caucasian men examined by DXA for suspected Op, no significant association was observed between Op and MetS. The study results contrast to those observed in women enrolled in the same geographical area, with identical criteria and in the same time range and may be related to sexual dimorphism occurring in clinical expressiveness of both MetS and Op.


Subject(s)
Absorptiometry, Photon , Metabolic Syndrome , Osteoporosis , Absorptiometry, Photon/methods , Absorptiometry, Photon/statistics & numerical data , Aged , Blood Glucose/metabolism , Bone Density/physiology , Cross-Sectional Studies , Humans , Independent Living/statistics & numerical data , Italy/epidemiology , Lumbar Vertebrae/diagnostic imaging , Male , Medical Records/statistics & numerical data , Metabolic Syndrome/diagnosis , Metabolic Syndrome/ethnology , Metabolic Syndrome/physiopathology , Negative Results , Osteoporosis/diagnosis , Osteoporosis/ethnology , Osteoporosis/metabolism , Risk Factors , Waist Circumference , White People
3.
J Endocrinol Invest ; 44(6): 1321-1326, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32960417

ABSTRACT

PURPOSE: Osteoporosis (Op) and metabolic syndrome (MetS) are two common disorders showing common pathogenic patterns. This cross-sectional study was performed to evaluate if MetS and its constitutive elements are associated to an increased risk of low bone mineral density (BMD) in free-living women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. METHODS: 13,182 free-living Caucasian women referring to "COMEGEN" general practitioners cooperative operating in Naples, Italy, performed a contextual evaluation of BMD by DXA and all MetS constitutive elements (systolic and diastolic blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose) between June 1st 2008 and May 31st 2018. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary Op were excluded from the study. RESULTS: MetS is associated to an increased risk of low BMD (Odds Ratio 1.19; 95% Confidence Interval 1.08-1.31). Among MetS constitutive elements, hypertension was associated to increased risk of low BMD, whereas high fasting glucose level/diabetes were associated to reduced risk of low BMD. CONCLUSIONS: The significant association between Op and MetS in free-living women examined by DXA for suspected Op suggests the advisability of a contextual evaluation of both disorders in this setting.


Subject(s)
Absorptiometry, Photon , Bone Diseases, Metabolic , Metabolic Syndrome , Absorptiometry, Photon/methods , Absorptiometry, Photon/statistics & numerical data , Blood Glucose/analysis , Bone Density/physiology , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/diagnosis , Bone Diseases, Metabolic/epidemiology , Cholesterol, HDL/blood , Cross-Sectional Studies , Female , Humans , Independent Living , Italy/epidemiology , Metabolic Syndrome/blood , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Middle Aged , Osteoporosis/diagnosis , Osteoporosis/metabolism , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk Factors , Triglycerides/blood , Waist Circumference
4.
Ultrasound Obstet Gynecol ; 55(3): 401-410, 2020 03.
Article in English | MEDLINE | ID: mdl-31237047

ABSTRACT

OBJECTIVE: To assess the accuracy of preoperative ultrasound examination for predicting lymph-node (LN) status in patients with vulvar cancer. METHODS: This was a single-institution retrospective observational study of all women with a histological diagnosis of vulvar cancer triaged to inguinal surgery within 30 days following ultrasound evaluation between December 2010 and January 2016. For each groin examined, 15 morphological and dimensional sonographic parameters associated with suspicion for LN involvement were examined. A morphometric ultrasound pattern (MUP) was expressed for each groin, classifying the inguinal LN status into five groups (normal; reactive-but-negative; minimally suspicious/probably negative; moderately suspicious; and highly suspicious/positive) according to subjective judgment, followed by stratification as positive or negative for metastasis according to morphometric binomial assessment (MBA). In cases of positive MBA, fine-needle aspiration cytology was performed. Combining the information obtained from MUP and cytologic results, a binomial final overall assessment (FOA) was assigned for each groin. The final histology was considered as the reference standard. Comparison was performed between patients with negative and those with positive LNs on histology, and receiver-operating-characteristics curves were generated for statistically significant variables on univariate analysis, to evaluate their diagnostic ability to predict negative LN status. RESULTS: Of 144 patients included in the analysis, 87 had negative inguinal LNs and 57 had positive LNs on histology. A total of 256 groins were analyzed, of which 171 were negative and 85 showed at least one metastatic LN on histology. The following parameters showed the greatest accuracy, with the best balance between specificity and sensitivity, in predicting negative LN status: cortical (C) thickness of the dominant LN (cut-off, 2.5 mm; sensitivity, 90.0%; specificity, 77.9%); short-axis (S) length of the dominant LN (cut-off, 8.4 mm; sensitivity, 63.9%; specificity, 90.6%); C/medulla (M) thickness ratio of the dominant LN (cut-off, 1.2 mm; sensitivity, 70.4%; specificity, 91.5%), the combination of S length and C/M thickness ratio (sensitivity, 88.9%; specificity, 82.4%); and the FOA analysis (sensitivity, 85.9%; specificity, 84.2%). CONCLUSIONS: Preoperative ultrasound assessment, with or without the addition of cytology, has a high accuracy in assessing inguinal LN status in patients with vulvar cancer. In particular, the combination of two ultrasound parameters (S length and C/M thickness ratio) provided the greatest accuracy in discriminating between negative and positive LNs. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Subject(s)
Biopsy, Fine-Needle/statistics & numerical data , Lymphatic Metastasis/diagnostic imaging , Preoperative Care/statistics & numerical data , Ultrasonography/statistics & numerical data , Vulvar Neoplasms/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle/methods , Female , Groin/diagnostic imaging , Groin/pathology , Humans , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Middle Aged , Predictive Value of Tests , Preoperative Period , Retrospective Studies , Sensitivity and Specificity , Ultrasonography/methods , Vulvar Neoplasms/pathology , Vulvar Neoplasms/surgery , Young Adult
5.
Br J Dermatol ; 170(5): 1151-7, 2014 May.
Article in English | MEDLINE | ID: mdl-24506834

ABSTRACT

BACKGROUND: Although the standard treatment for venous ulcers is compression, drugs may be used as adjunctive therapy. Simvastatin has shown potential wound-healing properties; however, no studies have investigated its use in venous ulcers. OBJECTIVES: To assess the efficacy and safety of simvastatin in venous ulcer healing when combined with standard treatment for ulcers. METHODS: This was a randomized, double-blind, placebo-controlled trial. Outcome measures were the proportion of healed ulcers, healing time, total surface area healed and Dermatology Life Quality Index (DLQI) scores. RESULTS: Sixty-six patients were randomized into two groups: a simvastatin (n = 32) and a control (n = 34) group. Among ulcers ≤ 5 cm, 100% were healed in the simvastatin group, and 50% were healed in the control group [relative risk (RR) 0·10, 95% confidence interval (CI) 0·0141-0·707]. The average healing times for ulcers ≤ 5 cm were 6·89 ± 0·78 weeks and 8·40 ± 1·13 weeks for the simvastatin and control groups, respectively (P < 0·001). Among ulcers > 5 cm, 67% closed in the simvastatin group, with a mean healing time of 9·17 ± 1·07 weeks. No ulcers of this size closed in the control group (RR 0·33, 95% CI 0·132-0·840). The simvastatin group had lower DLQI scores (P < 0·001) post-treatment. No adverse effects were documented. CONCLUSIONS: Simvastatin 40 mg daily, in addition to standard wound care and compression, is associated with a significant improvement in healing rate and time, as well as an improved patient quality of life when compared with placebo in the management of venous ulcers.


Subject(s)
Cardiovascular Agents/administration & dosage , Dermatologic Agents/administration & dosage , Simvastatin/administration & dosage , Varicose Ulcer/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Male , Middle Aged , Treatment Outcome , Wound Healing/drug effects , Young Adult
6.
Eur Arch Paediatr Dent ; 24(4): 499-505, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37347383

ABSTRACT

PURPOSE: To investigate the direct and indirect pathways between verbal bullying and adverse oral conditions among school-aged children. METHODS: A cross-sectional survey was conducted with 8- to 10-year-old children, enrolled in public schools in Southern Brazil. Verbal bullying was collected by self-reports. Independent variables included sociodemographic characteristics (sex, age, household income, and caregivers' educational level) and oral conditions (anterior open bite, anterior teeth crowding, upper anterior diastema, large overjet, untreated dental caries, and PUFA index). The pathways between verbal bullying and the independent variables were analysed through structural equation modelling. RESULTS: 1369 children were included. The prevalence of verbal bullying was 26.2% (95% confidence interval [CI] 23.9-28.6%). Verbal bullying was directly influenced by large overjet (standard coefficient [SC] 0.13, P < 0.01), untreated dental caries (SC 0.63, P = 0.01) and PUFA index (SC 0.75, P = 0.02). Sex (SC - 0.005, P = .04) and age (SC - 0.006, P < 0.01) indirectly influenced verbal bullying via untreated dental caries. CONCLUSIONS: Verbal bullying was directly influenced by large overjet, untreated dental caries and PUFA index. Sex and age indirectly impacted verbal bullying through untreated dental caries.


Subject(s)
Bullying , Dental Caries , Malocclusion , Mouth Diseases , Overbite , Humans , Child , Dental Caries/epidemiology , Cross-Sectional Studies , Prevalence , Brazil/epidemiology
7.
Int J Clin Pract ; 66(10): 969-75, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22994331

ABSTRACT

OBJECTIVE: To examine the demographic and psychopathological characteristics of the treatment discontinuation group compared with patients who completed with paliperidone ER treatment for 6 months. METHODS: A total of 984 patients meeting the DSM-IV criteria for schizophrenia who switched their antipsychotics were recruited from 61 sites in five countries in Southeast Asia. The patients with early discontinuation were then compared with those who completed the 6-month treatment in terms of demographic and psychopathological variables at baseline and also at the end of the evaluation period, which included PANSS score, sleep quality, daytime drowsiness, PSP score, ESRS score and clinical global impression-severity (CGI-S) score. Finally, logistic regression analysis was applied to determine predictive factors that were associated with discontinuation. RESULTS: Of 984 patients, 284 patients (28.9%) discontinued without completing the 6-month treatment period with paliperidone. Significant differences in patient baseline characteristics for the discontinuation group compared with the completion group were observed for gender, number of previous hospitalisations with psychosis, PANSS total score and all of its subscales, daytime drowsiness score, total ESRS score, CGI-S, PSP and Insight. Patients who completed the study period had significantly better scores in all psychopathology variables compared with the discontinuation group at the end of the evaluation period. Numbers of previous hospitalisations because of psychosis, being exposed with first generation antipsychotics, gender and PANSS total scores were found to be significant predictors of discontinuation. CONCLUSION: Patients who discontinued early from a 6-month treatment period with Paliperidone have some characteristic differences compared with completion patients. Many factors including frequent hospitalisations, female gender, high PANSS score (indicating more disease severity) and previous exposure to first generation of antipsychotic agent might lead patients to discontinue from treatment.


Subject(s)
Antipsychotic Agents/therapeutic use , Isoxazoles/therapeutic use , Pyrimidines/therapeutic use , Schizophrenia/drug therapy , Adult , Analysis of Variance , Drug Substitution , Female , Humans , Long-Term Care , Male , Paliperidone Palmitate , Prospective Studies , Psychopathology , Treatment Outcome
8.
Eur Arch Paediatr Dent ; 23(6): 911-918, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35904752

ABSTRACT

PURPOSE: Evaluate the impact of the premature loss of primary molars due to caries on oral health-related quality of life (OHRQoL) in schoolchildren. METHODS: A cross-sectional study was conducted with children eight to ten years of age at public schools in the city of Florianópolis selected through cluster sampling. The collection of the clinical data occurred in the school setting by four trained and calibrated examiners (Kappa > 0.7) DMFT/dmft index, PUFA/pufa index, accentuated overjet, and anterior open bite. Sex and age of the child and guardian's schooling (classified as ≤ 8 or > 8 years) were collected through a questionnaire answered by the guardians. OHRQoL was assessed using the Child Perceptions Questionnaire 8-10. The data were submitted to bivariate, multivariate, and hierarchical Poisson analyses. RESULTS: A total of 1456 children participated in the study. The prevalence of premature tooth loss due to caries was 5.8% (n = 85). The prevalence of negative impact on OHRQoL was 47.4% (n = 691). Negative impact on OHRQoL was significantly associated with the premature loss of primary molars (p < 0.001) as well as the sex (girls), guardian's schooling (> 8 years) and the presence of untreated caries (p < 0.001). CONCLUSION: The premature loss of primary molars due to caries was associated a negative impact on the OHRQoL of children eight to ten years of age. Negative impact is also associated with untreated caries, sex, and the level of schooling of guardians.


Subject(s)
Dental Caries , Quality of Life , Child , Female , Humans , Oral Health , Cross-Sectional Studies , Dental Caries/epidemiology , Surveys and Questionnaires , Prevalence , Molar , Brazil/epidemiology
9.
Eur Rev Med Pharmacol Sci ; 15(12): 1461-72, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22288307

ABSTRACT

NSAIDs are generally considered to be safe and well tolerated, but, even with the advent of selective COX-2 inhibitors, nephrotoxicity remains a concern. An impaired renal perfusion caused by the inhibition of prostaglandin synthesis is claimed like the more frequent cause of an acute renal failure due to NSAIDs, while a chronic interstitial nephritis or an analgesic nephropathy are believed the causes of a chronic renal failure. The real incidence of renal side effects of NSAIDs is still unclear and it differs between the age of the patients and the reports present in the literature. The occurrence of renal side effects following prenatal exposure to NSAIDs seems to be rare considering the large number of pregnant woman treated with indomethacin or other prostaglandin inhibitors. NSAID-related nephrotoxicity remains an important clinical problem in the newborns, in whom the functionally immature kidney may exert a significant effect on the disposition of the drugs. Instead, nephrotoxicity is a rare event in children and the risk is lower than adults. In healthy adult patients the incidence of renal adverse effects is very low, less than 1%. The risk increased with age. The elderly are at higher risk, and it is correlated at the presence of pretreatment renal disease, hypovolemia due to use of diuretics, diabetes, congestive heart failure or alteration of NSAID pharmacokinetics.


Subject(s)
Acute Kidney Injury/chemically induced , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Indomethacin/adverse effects , Acute Kidney Injury/epidemiology , Acute Kidney Injury/pathology , Adult , Age Factors , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Child , Female , Humans , Indomethacin/administration & dosage , Indomethacin/pharmacokinetics , Infant, Newborn , Pregnancy , Prenatal Exposure Delayed Effects , Risk Factors
10.
Braz J Biol ; 80(2): 336-344, 2020.
Article in English | MEDLINE | ID: mdl-31596357

ABSTRACT

Although the potential of surrogate propagation technology for aquaculture and conservation of Neotropical fish, the poor understanding of the host immune system may results in rejection and destruction of the donor material. Thus, it is necessary to study and to develop methods to evaluate the effects of immunosuppressive drugs employment and to evaluate the immunocompatibility between donor and receptor. Thus, the present study aimed to optimize a methodology to assess in vivo phagocytosis in Astyanax altiparanae using Saccharomyces cerevisiae and to evaluate their hematological response resultant from the inflammatory induction. To this, S. cerevisiae were labeled with Congo red and injected in the coelomic cavity of A. altiparanae at the concentration of 2.5 x 106 cells mL-1. A PBS solution and a non-injected group were kept as control. Fish blood was sampled and the phagocytic capacity and index were determined at 1, 2, 3 and 6 h post-injection (hpi). The yeast injection successfully stimulated phagocytosis, with the best result for phagocytosis assessment after 2 hpi. Moreover, it was achieved a high traceability of phagocytized and non-phagocytized yeast under optic microscopy analysis due to the Congo red labeling. The hematological profile was similar to usually observed in early infections, indicating lymphocyte migration to inflammatory site and increase in number of circulating phagocytes due to natural response to inflammatory stimulus. In conclusion, our method was efficient to assess in vivo phagocytosis in A. altiparanae and will be an important tool to evaluate the efficacy of immunosuppressive drugs in this species. Additionally, these results may serve as support for further studies in fish immunocompetence, both in laboratory and in field conditions.


Subject(s)
Characidae , Hematology , Animals , Aquaculture , Phagocytosis , Saccharomyces cerevisiae
11.
J Cell Biol ; 144(5): 947-61, 1999 Mar 08.
Article in English | MEDLINE | ID: mdl-10085293

ABSTRACT

Alignment of the mitotic spindle with the axis of cell division is an essential process in Saccharomyces cerevisiae that is mediated by interactions between cytoplasmic microtubules and the cell cortex. We found that a cortical protein, the yeast formin Bni1p, was required for spindle orientation. Two striking abnormalities were observed in bni1Delta cells. First, the initial movement of the spindle pole body (SPB) toward the emerging bud was defective. This phenotype is similar to that previously observed in cells lacking the kinesin Kip3p and, in fact, BNI1 and KIP3 were found to be in the same genetic pathway. Second, abnormal pulling interactions between microtubules and the cortex appeared to cause preanaphase spindles in bni1Delta cells to transit back and forth between the mother and the bud. We therefore propose that Bni1p may localize or alter the function of cortical microtubule-binding sites in the bud. Additionally, we present evidence that other bipolar bud site determinants together with cortical actin are also required for spindle orientation.


Subject(s)
Fungal Proteins/physiology , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae/cytology , Spindle Apparatus/physiology , Actins/metabolism , Base Sequence , Binding Sites , DNA Primers , Fungal Proteins/metabolism , Microfilament Proteins/metabolism , Microfilament Proteins/physiology , Microscopy, Fluorescence , Microtubules , Molecular Sequence Data , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/physiology
12.
J Cell Biol ; 141(6): 1357-70, 1998 Jun 15.
Article in English | MEDLINE | ID: mdl-9628892

ABSTRACT

The budding yeast contains two type I myosins, Myo3p and Myo5p, with redundant functions. Deletion of both myosins results in growth defects, loss of actin polarity and polarized cell surface growth, and accumulation of intracellular membranes. Expression of myc-tagged Myo5p in myo3Delta myo5Delta cells fully restores wild-type characteristics. Myo5p is localized as punctate, cortical structures enriched at sites of polarized cell growth. We find that latrunculin-A-induced depolymerization of F-actin results in loss of Myo5p patches. Moreover, incubation of yeast cells at 37 degrees C results in transient depolarization of both Myo5p patches and the actin cytoskeleton. Mutant Myo5 proteins with deletions in nonmotor domains were expressed in myo3Delta myo5Delta cells and the resulting strains were analyzed for Myo5p function. Deletion of the tail homology 2 (TH2) domain, previously implicated in ATP-insensitive actin binding, has no detectable effect on Myo5p function. In contrast, myo3Delta myo5Delta cells expressing mutant Myo5 proteins with deletions of the src homology domain 3 (SH3) or both TH2 and SH3 domains display defects including Myo5p patch depolarization, actin disorganization, and phenotypes associated with actin dysfunction. These findings support a role for the SH3 domain in Myo5p localization and function in budding yeast. The proline-rich protein verprolin (Vrp1p) binds to the SH3 domain of Myo3p or Myo5p in two-hybrid tests, coimmunoprecipitates with Myo5p, and colocalizes with Myo5p. Immunolocalization of the myc-tagged SH3 domain of Myo5p reveals diffuse cytoplasmic staining. Thus, the SH3 domain of Myo5p contributes to but is not sufficient for localization of Myo5p either to patches or to sites of polarized cell growth. Consistent with this, Myo5p patches assemble but do not localize to sites of polarized cell surface growth in a VRP1 deletion mutant. Our studies support a multistep model for Myo5p targeting in yeast. The first step, assembly of Myo5p patches, is dependent upon F-actin, and the second step, polarization of actin patches, requiresVrp1p and the SH3 domain of Myo5p.


Subject(s)
Actins/metabolism , Fungal Proteins/metabolism , Microfilament Proteins/metabolism , Myosin Type I , Myosins/metabolism , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae/metabolism , src Homology Domains , Cell Division , Cytoskeleton/physiology , Fungal Proteins/genetics , Mutagenesis , Myosins/genetics , Proline/metabolism , Saccharomyces cerevisiae/genetics , Temperature
13.
J Cell Biol ; 148(2): 353-62, 2000 Jan 24.
Article in English | MEDLINE | ID: mdl-10648568

ABSTRACT

Type I myosins are highly conserved actin-based molecular motors that localize to the actin-rich cortex and participate in motility functions such as endocytosis, polarized morphogenesis, and cell migration. The COOH-terminal tail of yeast myosin-I proteins, Myo3p and Myo5p, contains an Src homology domain 3 (SH3) followed by an acidic domain. The myosin-I SH3 domain interacted with both Bee1p and Vrp1p, yeast homologues of human WASP and WIP, adapter proteins that link actin assembly and signaling molecules. The myosin-I acidic domain interacted with Arp2/3 complex subunits, Arc40p and Arc19p, and showed both sequence similarity and genetic redundancy with the COOH-terminal acidic domain of Bee1p (Las17p), which controls Arp2/3-mediated actin nucleation. These findings suggest that myosin-I proteins may participate in a diverse set of motility functions through a role in actin assembly.


Subject(s)
Actins/physiology , Cytoskeletal Proteins , Molecular Motor Proteins/physiology , Myosin Type I , Myosins/physiology , Saccharomyces cerevisiae Proteins , Actin-Related Protein 2 , Actin-Related Protein 3 , Actins/metabolism , Amino Acid Sequence , Cell Movement/physiology , Fungal Proteins/metabolism , Ligands , Microfilament Proteins/metabolism , Models, Biological , Molecular Sequence Data , Morphogenesis/physiology , Myosin Heavy Chains/metabolism , Myosins/metabolism , Protein Binding , Proteins/metabolism , Saccharomyces cerevisiae , Two-Hybrid System Techniques , Wiskott-Aldrich Syndrome Protein
14.
Science ; 276(5309): 118-22, 1997 Apr 04.
Article in English | MEDLINE | ID: mdl-9082982

ABSTRACT

The Saccharomyces cerevisiae BNI1 gene product (Bni1p) is a member of the formin family of proteins, which participate in cell polarization, cytokinesis, and vertebrate limb formation. During mating pheromone response, bni1 mutants showed defects both in polarized morphogenesis and in reorganization of the underlying actin cytoskeleton. In two-hybrid experiments, Bni1p formed complexes with the activated form of the Rho-related guanosine triphosphatase Cdc42p, with actin, and with two actin-associated proteins, profilin and Bud6p (Aip3p). Both Bni1p and Bud6p (like Cdc42p and actin) localized to the tips of mating projections. Bni1p may function as a Cdc42p target that links the pheromone response pathway to the actin cytoskeleton.


Subject(s)
Actins/metabolism , Cell Cycle Proteins/metabolism , Contractile Proteins , Cytoskeleton/metabolism , Fungal Proteins/metabolism , GTP-Binding Proteins/metabolism , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/metabolism , Fungal Proteins/genetics , Microfilament Proteins/metabolism , Morphogenesis , Mutagenesis , Profilins , Recombinant Fusion Proteins/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/growth & development , Signal Transduction , cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
15.
Science ; 294(5550): 2364-8, 2001 Dec 14.
Article in English | MEDLINE | ID: mdl-11743205

ABSTRACT

In Saccharomyces cerevisiae, more than 80% of the approximately 6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of approximately 4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis of genes with roles in cytoskeletal organization (BNI1, ARP2, ARC40, BIM1), DNA synthesis and repair (SGS1, RAD27), or uncharacterized functions (BBC1, NBP2) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.


Subject(s)
Cytoskeletal Proteins , Gene Deletion , Genes, Fungal/physiology , Genetic Techniques , Microfilament Proteins , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/physiology , Carrier Proteins/genetics , Carrier Proteins/physiology , Cell Cycle Proteins/genetics , Cell Cycle Proteins/physiology , Cell Polarity , Computational Biology , Crosses, Genetic , Cytoskeleton/physiology , DNA Helicases/genetics , DNA Helicases/physiology , DNA Repair , DNA, Fungal/biosynthesis , Databases, Genetic , Endodeoxyribonucleases/genetics , Endodeoxyribonucleases/physiology , Flap Endonucleases , Fungal Proteins/genetics , Fungal Proteins/physiology , Genes, Essential , Genetic Markers , Genome, Fungal , Microtubule Proteins/genetics , Microtubule Proteins/physiology , Mitosis , RecQ Helicases , Recombination, Genetic , Robotics , Saccharomyces cerevisiae/growth & development , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/physiology
16.
Eur Rev Med Pharmacol Sci ; 23(4 Suppl): 5-13, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31755079

ABSTRACT

Musculoskeletal pain, encompassing back and osteoarthritis (OA) pain, represents the most frequent source of chronic pain in western countries, and it is particularly frequent in older adults. Remarkably, back and OA pain present, in most cases, both a nociceptive and a neuropathic component of pain. Treatment selection should, therefore, properly consider the ability of a drug to act on both components, reducing the possibility of plastic changes in the central nervous system, and consequently promoting physical rehabilitation. The pharmacological profile of tapentadol, combining synergistically µ-opioid receptor (MOR) agonist and norepinephrine reuptake inhibition (NRI) in one single molecule with a concomitant reduction in the burden of adverse events, is unique, to date, and makes this drug particularly suitable for the treatment of back pain and OA-associated pain, especially when a neuropathic component is present. Tapentadol is an innovative dual-acting analgesic molecule, which combines two mechanisms of action, namely MOR agonism and NRI. This narrative review will briefly discuss the pharmacological action of tapentadol and its rationale for use in back pain and OA.


Subject(s)
Analgesics, Opioid/administration & dosage , Musculoskeletal Pain/drug therapy , Tapentadol/administration & dosage , Therapies, Investigational/methods , Analgesics, Opioid/metabolism , Chronic Pain , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/metabolism , Humans , Musculoskeletal Pain/metabolism , Randomized Controlled Trials as Topic/methods , Tapentadol/metabolism , Therapies, Investigational/trends , Treatment Outcome
17.
Sci Robot ; 4(32)2019 Jul 17.
Article in English | MEDLINE | ID: mdl-33137771

ABSTRACT

Targeted muscle reinnervation (TMR) amplifies the electrical activity of nerves at the stump of amputees by redirecting them in remnant muscles above the amputation. The electrical activity of the reinnervated muscles can be used to extract natural control signals. Nonetheless, current control systems, mainly based on noninvasive muscle recordings, fail to provide accurate and reliable control over time. This is one of the major reasons for prosthetic abandonment. This prospective interventional study includes three unilateral above-elbow amputees and reports the long-term (2.5 years) implant of wireless myoelectric sensors in the reinnervation sites after TMR and their use for control of robotic arms in daily life. It therefore demonstrates the clinical viability of chronically implanted myoelectric interfaces that amplify nerve activity through TMR. The patients showed substantial functional improvements using the implanted system compared with control based on surface electrodes. The combination of TMR and chronically implanted sensors may drastically improve robotic limb replacement in above-elbow amputees.

18.
Vet Rec ; 180(24): 592, 2017 Jun 17.
Article in English | MEDLINE | ID: mdl-28341722

ABSTRACT

The aim of this study was to determine the onset and offset of antinociception after sciatic (ScN) and femoral (FN) nerve blocks. Six healthy adult cats (4.8±1.3years; 4.3±0.4 kg) were included in a randomised, crossover, blinded and controlled study. Following sedation with dexmedetomidine (25 µg/kg, intramuscular), each ScN and FN injection was performed using 0.1 ml/kg of saline (CONTROL), bupivacaine (0.46 per cent, 0.46 mg/kg; BUPI), bupivacaine and dexmedetomidine (1 µg/kg; BUPI-DEX) or bupivacaine and buprenorphine (2.5 µg/kg; BUPI-BUPRE). Atipamezole (250 µg/kg) was administered after injections. Paw withdrawal thresholds (PWT) and motor blockade were evaluated before sedation and up to 24 hours. The PWT were significantly increased at half an hour in CONTROL, from two to four hours in BUPI and BUPI-DEX when compared with baseline. Motor blockade was observed between one and three hours in treatments using bupivacaine. Ability to walk was significantly impaired in BUPI at half an hour to two hours, BUPI-DEX at one to two hours and BUPI-BUPRE at two hours. Antinociception was observed in BUPI between one and eight hours, and in BUPI-DEX and BUPI-BUPRE between one and four hours. This study could not demonstrate a benefit of administering bupivacaine with dexmedetomidine or buprenorphine in cats. Results in BUPI-DEX may have been biased by the administration of atipamezole.


Subject(s)
Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Buprenorphine/administration & dosage , Dexmedetomidine/administration & dosage , Femoral Nerve , Nerve Block/veterinary , Sciatic Nerve , Animals , Cats , Cross-Over Studies , Drug Therapy, Combination/veterinary , Female , Male , Nerve Block/methods
19.
Article in English | MEDLINE | ID: mdl-28596903

ABSTRACT

BACKGROUND: Latin America Treatment and Innovation Network in Mental Health (LATIN-MH) is a research hub located in Brazil and Peru that conducts a research project to help reduce the treatment gap in mental health in Latin America (LA). Besides its research core, LATIN-MH has a Capacity Building (CB) component that aims to help young researchers receive the specific training to contribute to the growing scientific production in mental health in LA. METHODS: LATIN-MH proposal in CB includes a series of actions to prepare professionals in the research area. The main proposals are described here, which include online study groups, promotion of scientific meetings, hands-on training in different levels and sharing of information. RESULTS: LATIN-MH CB activities are at its initial stages but the proposed activities were well evaluated by the participants. The first participating fellows who finished their fellowships are contributing elsewhere in the mental treatment and human resources formation area. CONCLUSION: The repercussion of LATIN-MH actions in CB and its evaluation, particularly on the formation of human resources and dissemination of information, show that the hub is contributing to the critic formation of young researchers and the circulation of important information.

20.
Eur J Surg Oncol ; 43(9): 1776-1783, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28751058

ABSTRACT

OBJECTIVE: The study aims were: 1) to verify the role of sentinel node biopsy (SNB) in a subset of patients with clinical N0 (cN0) invasive vulvar cancer (VC) who were still candidates for radical inguinal surgery according to the current guidelines; 2) to investigate whether a preoperative 18F-FDG PET/CT (PET/CT) evaluation could improve the selection of node negative patients. METHODS: From July 2013 to July 2016, all patients with VC admitted to our Division were evaluated by standard imaging and clinical exam. Among the patients assessed as cN0 we enrolled those unsuitable for SNB, due to: T > 4 cm, multifocal tumors, complete tumor diagnostic excision, contralateral nodal involvement and local recurrence. A preoperative PET/CT was performed. For each patient surgery included SNB, performed using a combined technique (radiotracer plus blue dye), followed by standard inguino-femoral lymphadenectomy. The reference standard was histopathology. RESULTS: Forty-seven patients entered the study for a total of 73 groins. Histopathology revealed 12 metastatic SNs in 9 groins. No false negative SNs were found (NPV 100%). PET/CT showed a negative predictive value of 93%. CONCLUSIONS: Our data suggest that SNB is accurate and safe even in cN0 patients currently excluded from this procedure, providing that a careful preoperative selection is performed. PET/CT allows a reliable assessment of LN status and may be an effective support for the selection of patients who are safe candidates for SNB.


Subject(s)
Carcinoma/surgery , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Positron Emission Tomography Computed Tomography , Sentinel Lymph Node Biopsy , Vulvar Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma/diagnostic imaging , Carcinoma/secondary , Female , Fluorodeoxyglucose F18 , Humans , Inguinal Canal , Lymph Nodes/surgery , Lymphatic Metastasis , Middle Aged , Minimally Invasive Surgical Procedures , Neoplasm Invasiveness , Neoplasm Staging , Patient Selection , Pilot Projects , Predictive Value of Tests , Preoperative Period , Prospective Studies , Radiopharmaceuticals , Vulvar Neoplasms/diagnostic imaging , Vulvar Neoplasms/pathology
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