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1.
J Nutr Health Aging ; 28(7): 100282, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38833764

ABSTRACT

OBJECTIVES: This study aimed to assess the prevalence and impact of loneliness (De Jong Gierveld scale) and isolation (Lubben scale) on the effects of a hospital-based exercise programme. DESIGN: Secondary analysis of a randomised clinical trial. SETTING: Acute Geriatric Unit of a tertiary hospital in Spain. PARTICIPANTS: 103 hospitalised older adults. INTERVENTION: Individualised multicomponent exercise program (20-minute sessions twice a day for 3 consecutive days). RESULTS: Among the 103 randomised patients included in the analysis (both arms included), 58.3% were male, and their mean age was 87.3 (4.5) years. According to the Lubben scale, 15.8% of patients were at risk of isolation, while 62.7% were in a situation of severe or moderate loneliness according to the De Jong Gierveld scale. In the non-isolated group, training showed a substantial positive impact on Geriatric Depression Scale (B = -1.25, 95% CI = -0.24 to -0.27). In the isolated group, all outcomes improved, but only the Quality of Life showed significant changes (B = 35, 95% CI = 4.96-35.8). The SPPB test (B = 1.62, 95% CI = 0.19-3.04) and Quality of Life, (B = 17.1, 95% CI = 1.84-32.3) showed a significant improvement in the non-loneliness exercise group while no differences were found in the loneliness group. CONCLUSION: Despite the high prevalence of loneliness and social isolation, individualised exercise programs provide significant benefits to hospitalised patients, especially in quality of life.

2.
Virol J ; 20(1): 123, 2023 06 13.
Article in English | MEDLINE | ID: mdl-37312093

ABSTRACT

BACKGROUND: Elite controllers are able to control viral replication without antiretroviral therapy. Exceptional elite controllers do not show disease progression for more than 25 years. Different mechanisms have been proposed and several elements of both innate and adaptive immunity are implicated. Vaccines are immune stimulating agents that can promote HIV-RNA transcription; transient plasma HIV-RNA detectability has been described within 7-14 days after different vaccinations. The most reliable mechanism involved in virosuppressed people living with HIV is a generalized inflammatory response that activates bystander cells harboring latent HIV. So far no data about viral load increase in elite controllers after SARS-CoV-2 vaccination are reported in literature. CASE PRESENTATION: We report the case of a 65-year-old woman of European ancestry, diagnosed with HIV-1/HCV co-infection more than 25 years ago. Since then, HIV-RNA remained undetectable and she never received ARV therapy. In 2021 she was vaccinated with mRNA-BNT162b2 vaccine (Pfizer-BioNTech®). She was administered with three doses in June, July and October 2021, respectively. The last available viral load was undetectable in March 2021. We observed an increase of VL at 32 cp/ml and 124 cp/mL, two and seven months after the second vaccine dose, respectively. During monthly follow-up, HIV-RNA gradually and spontaneously dropped becoming undetectable without ARV intervention. COVID-19 serology was positive with IgG 535 BAU/mL, showing response to vaccination. We measured total HIV-DNA at different time-points and we found it detectable both at the time of the higher plasma HIV-RNA (30 cp/10^6 PBMCs) and when it was undetectable (13 cp/10^6 PBMCs), in reduction. CONCLUSIONS: This case is the first report, to our knowledge, describing a rebound of plasma HIV-RNA in an elite controller after three doses of mRNA-BNT162b2 vaccine for SARS-CoV-2. Concomitantly with a spontaneous reduction of plasma HIV-RNA ten months after the third dose of mRNA-BNT162b2 vaccine (Pfizer-BioNTech®) without antiretroviral therapy intervention, we observed a reduction of total HIV-DNA in peripheral mononuclear cells. The potential role of vaccinations in altering HIV reservoir, even in elite controllers when plasma HIV-RNA is undetectable, could be a valuable aspect to take into account for the future HIV eradication interventions.


Subject(s)
COVID-19 , HIV Infections , HIV Seropositivity , HIV-1 , Female , Humans , Aged , HIV Infections/drug therapy , COVID-19 Vaccines , BNT162 Vaccine , SARS-CoV-2 , COVID-19/prevention & control , Virus Latency , Vaccination , Elite Controllers , RNA, Messenger
3.
Rev Sci Instrum ; 94(3): 033903, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-37012774

ABSTRACT

Here, we present an integrated ultra-high-vacuum (UHV) apparatus for the growth of complex materials and heterostructures. The specific growth technique is the Pulsed Laser Deposition (PLD) by means of a dual-laser source based on an excimer KrF ultraviolet and solid-state Nd:YAG infra-red lasers. By taking advantage of the two laser sources-both lasers can be independently used within the deposition chambers-a large number of different materials-ranging from oxides to metals, to selenides, and others-can be successfully grown in the form of thin films and heterostructures. All of the samples can be in situ transferred between the deposition chambers and the analysis chambers by using vessels and holders' manipulators. The apparatus also offers the possibility to transfer samples to remote instrumentation under UHV conditions by means of commercially available UHV-suitcases. The dual-PLD operates for in-house research as well as user facility in combination with the Advanced Photo-electric Effect beamline at the Elettra synchrotron radiation facility in Trieste and allows synchrotron-based photo-emission as well as x-ray absorption experiments on pristine films and heterostructures.

4.
Epilepsy Behav ; 140: 109117, 2023 03.
Article in English | MEDLINE | ID: mdl-36804846

ABSTRACT

BACKGROUND: Psychogenic Non-Epileptic Seizures (PNES) and Functional Motor Disorders (FMDs) commonly represent the main clinical manifestations of Functional Neurological Disorders (FNDs). Despite their high prevalence in pediatric neurological services, literature on this topic is still spare for this population. The present study aimed to deepen the clinical knowledge of a pediatric FNDs sample through a demographic and clinical characterization of the most recurrent clinical patterns during the pediatric age. Moreover, a comparison of neuropsychological and psychopathological profiles of PNES and FMD patients was carried out to identify specific vulnerabilities and therapeutic targets linked with these different clinical manifestations. MATERIALS AND METHODS: A total of 43 FNDs patients (age range 7-17 years old) were retrospectively included in our study, enrolled in two subgroups: 20 with FMDs and 23 with PNES diagnosis. They were inpatients and outpatients referred over a period of 5 years and a standardized neurological, neuropsychological (WISC-IV/WAIS-IV), and psychiatric (CDI-2, MASC-2, ADES, DIS-Q, PID-5) evaluation was assessed. RESULTS: In PNES patients the most common clinical phenotypes were functional tonic-clonic (52%) and atonic (32%) manifestations while in the FMDs group were gait alterations (60%), functional myoclonus (35%), and tremor (35%). A higher frequency of cognitive impairment was reported in PNES patients with higher anxiety-depressive symptom rates than FMDs patients. CONCLUSIONS: Notably, specific neurocognitive and psychopathological profiles were described in PNES and FMDs, highlighting higher cognitive and psychiatric vulnerabilities in PNES, suggesting as well different strategy for therapeutic approaches.


Subject(s)
Conversion Disorder , Motor Disorders , Humans , Motor Disorders/diagnosis , Retrospective Studies , Seizures/complications , Seizures/diagnosis , Conversion Disorder/complications , Conversion Disorder/diagnosis , Anxiety/psychology , Electroencephalography
6.
Clin Ter ; 173(4): 301-303, 2022.
Article in English | MEDLINE | ID: mdl-35857045

ABSTRACT

Abstract: Autopsy has played an extremely important role in both the forensic and clinical fields for many years. In recent years, clinical autopsy has become less important, but today, thanks to the pandemic, this importance has been rediscovered. Conversely, forensic autopsy has never lost its importance, but it would need to be updated.


Subject(s)
Forensic Medicine , Pandemics , Autopsy , Humans
7.
J Helminthol ; 96: e12, 2022 Feb 23.
Article in English | MEDLINE | ID: mdl-35195063

ABSTRACT

The prevalence of vector-associated parasitic infections is high in central-southern Italy. The deltaic coastal plain of the Volturno River has been suspected, by veterinary practitioners, to have a high accidental incidence of Dirofilaria repens. Thus, the goal of this study was to evaluate the prevalence of dirofilariasis and other coinfections frequently described in dogs living in the Volturno area. Blood samples of 100 clinical asymptomatic dogs were examined using a Knott's technique and polymerase chain reaction in order to identify microfilariae. Other vector-borne coinfections were also investigated using ELISA kits. The results were analysed using statistical and Geographic Information System (GIS) software. Microfilariae of D. repens were detected in 10% of the dogs surveyed, with a presence of antibodies against Ehrlichia canis (4/10) and Dirofilaria immitis (1/10). Such high incidence should be considered in light of the zoonotic potential for D. repens and the support for more regular use of repellents to prevent the spread of this disease. The GIS analyses indicated that the study area provides suitable conditions to sustain populations of mosquito vectors and D. repens parasites throughout much of the year.


Subject(s)
Dirofilaria immitis , Dirofilaria repens , Dirofilariasis , Dog Diseases , Animals , Dirofilariasis/parasitology , Dog Diseases/epidemiology , Dog Diseases/parasitology , Dogs , Italy/epidemiology , Prevalence
8.
ESMO Open ; 6(4): 100171, 2021 08.
Article in English | MEDLINE | ID: mdl-34139487

ABSTRACT

BACKGROUND: Pheochromocytoma and paraganglioma (PPGL) have currently only limited treatment options available for patients in the metastatic phase (mPPGL) in either post-surgery or inoperable settings. However, these rare tumors overexpress somatostatin receptors and can thus be treated with peptide receptor radionuclide therapy (PRRT). We present data about our 10-year experience treating 46 consecutive mPPGL patients with 90Y-DOTATOC or 177Lu-DOTATATE. PATIENTS AND METHODS: All patients (20 men and 26 women, median age 52 years) showed positive scintigraphic imaging at 111In-octreotide or 68Ga-DOTATOC positron emission tomography/computed tomography (PET/CT). 90Y-DOTATOC was administered in 12 patients, with cumulative dosages ranging from 7.4 to 11 GBq, while 34 patients received 18.5 or 27.5GBq of 177Lu-DOTATATE. We used Southwest Oncology Group Response Evaluation Criteria in Solid Tumors criteria to evaluate treatment efficacy and Common Terminology Criteria for Adverse Events criteria to assess toxicity. The prognostic role of primary tumor site, hormone secretion, succinate dehydrogenase (SDHx) mutation, and metastatic involvement was also evaluated. RESULTS: Both 90Y-DOTATOC and 177Lu-DOTATATE PRRT were well tolerated by patients without significant renal or bone marrow toxicity. The median follow-up was 73 months (range 5-146 months). The overall disease control rate (DCR) was 80% [95% confidence interval (CI) 68.9% to 91.9%] with a mean five cycles of therapy. However, 177Lu-DOTATATE patients showed a longer median overall survival (mOS) than those receiving 90Y-Dotatoc and a better DCR when higher dosages were administered, even if a direct comparison was not carried out. Syndromic patients had a poorer mOS. SDHx mutations did not interfere with treatment efficacy. CONCLUSIONS: PRRT is safe and effective for the treatment of patients with progressive mPPGL, especially at higher dosages. The longer mOS of 177Lu-DOTATATE-treated patients in our protocols indicates the former radiopharmaceutical as the better candidate for further clinical application.


Subject(s)
Adrenal Gland Neoplasms , Neuroendocrine Tumors , Paraganglioma , Pheochromocytoma , Adrenal Gland Neoplasms/radiotherapy , Biomarkers , Female , Humans , Male , Middle Aged , Paraganglioma/diagnostic imaging , Paraganglioma/radiotherapy , Pheochromocytoma/radiotherapy , Positron Emission Tomography Computed Tomography , Prognosis , Receptors, Somatostatin , Yttrium Radioisotopes
10.
Plasmid ; 111: 102532, 2020 09.
Article in English | MEDLINE | ID: mdl-32853586

ABSTRACT

In this study we describe the genetic elements and the antimicrobial resistance units (RUs) harboured by the Salmonella Typhimurium monophasic variant 1,4,[5],12:i:- strain ST1030. Of the three identified RUs two were chromosomal, RU1 (IS26-blaTEM-1-IS26-strAB-sul2- IS26) and RU2 (IS26-tetR(B)-tetA(B)-ΔIS26), and one, RU3 (a sul3-associated class 1 integron with cassette array dfrA12-orfF-aadA2-cmlA1-aadA1), was embedded in a Tn21-derived element harboured by the conjugative I1 plasmid pST1030-1A. IS26 elements mediated the antimicrobial resistance gene (ARG) shuffling and this gave rise to pST1030-1A derivatives with different sets of ARGs. ST1030 also harboured two ColE1-like plasmids of which one, pST1030-2A, was mobilisable and the target of an intracellular translocation of the Tn21-derived element; the second (pST1030-3) was an orphan mob-associated oriT plasmid co-transferred with pST1030-1A and pST1030-2A. pST1030-2A and pST1030-3 also carried a parA gene and a type III restriction modification system, respectively. Overall analysis of our data reinforces the role played by IS26, Tn21-derived elements and non-conjugative plasmids in the spread of ARGs and supplies the first evidence, at least in Salmonella, for the identification of a natural isolate harbouring a three-element mobilisation system in the same cell.


Subject(s)
Anti-Bacterial Agents/pharmacology , DNA Transposable Elements , Drug Resistance, Bacterial , Genes, Bacterial , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Chromosome Mapping , Computational Biology/methods , Conjugation, Genetic , Genomics/methods , High-Throughput Nucleotide Sequencing , Microbial Sensitivity Tests , Molecular Sequence Annotation , Open Reading Frames , Plasmids/genetics
11.
Rev Med Liege ; 75(7-8): 497-500, 2020 Jul.
Article in French | MEDLINE | ID: mdl-32779897

ABSTRACT

We report a rare type of stress fracture in a young athlete, great hope of belgian table tennis. Although this type of fracture is not rare in the broad sense of the term, a stress fracture located at the distal femoral physeal is exceptional. Such a complication must be quickly detected because of growth disorders and impact on sports performances that this may cause. On the basis of an anamnesis and detailed clinical observations, we describe the physiopathology as well as the diagnostic and therapeutic management of this pathology.


Nous présentons un type rare de fracture de fatigue chez un jeune sportif, grand espoir du tennis de table belge. Bien que ce type de fracture ne soit pas rare au sens large du terme, une fracture de fatigue située au niveau du cartilage de croissance fémoral distal est exceptionnelle. Cette complication doit être rapidement détectée vu les troubles de croissance et l'impact sur les performances sportives que cela peut engendrer. A partir d'une anamnèse et d'observations cliniques minutieuses, nous décrivons la physiopathologie ainsi que la prise en charge diagnostique et thérapeutique de cette pathologie.


Subject(s)
Femoral Fractures , Fractures, Stress , Tennis , Belgium , Growth Plate , Humans , Tennis/injuries
12.
HIV Med ; 21(8): 523-535, 2020 09.
Article in English | MEDLINE | ID: mdl-32578947

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI). METHODS: This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of < 50 HIV-1 RNA copies/mL); (2) virologic failure [> 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR. RESULTS: In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR. CONCLUSIONS: Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients.


Subject(s)
Anti-HIV Agents/therapeutic use , Central Nervous System Diseases/etiology , HIV Infections/drug therapy , HIV-1/genetics , Acute Disease , Adult , Anti-HIV Agents/pharmacology , CD4 Lymphocyte Count , Female , HIV Infections/blood , HIV Infections/virology , HIV-1/drug effects , Humans , Italy , Male , Middle Aged , RNA, Viral/genetics , Regression Analysis , Retrospective Studies , Risk Factors , Treatment Failure , Viral Load/drug effects
13.
J Antimicrob Chemother ; 75(7): 1969-1971, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32211890

ABSTRACT

OBJECTIVES: An unexpected drug-drug interaction has been recently reported between dolutegravir, an HIV integrase inhibitor, and valproic acid. Despite there being several potential underlying mechanisms, plasma protein displacement has been suggested. The aim of this study was to assess plasma concentrations of several antiretrovirals when administered with or without valproic acid. METHODS: We performed a therapeutic drug monitoring registry analysis and identified patients concomitantly taking antiretrovirals and valproic acid and without clinical affecting conditions or interacting drugs. RESULTS: One hundred and thirty-four patients were identified. Median (IQR) age and BMI were 49.7 years (45-56) and 23.4 kg/m2 (20.8-26.3) and 78 were male (58.2%). Despite small groups, we observed no major effect on antiretroviral exposure, even when considering highly protein-bound compounds (such as etravirine), with the exception of dolutegravir trough concentrations [median (IQR) = 132 ng/mL (62-227) in individuals on valproic acid versus 760 ng/mL (333-1407) in those not receiving valproic acid]. CONCLUSIONS: Valproic acid does not have a major effect on antiretrovirals other than dolutegravir. The mechanism of this unexpected drug-drug interaction may be the combination of protein displacement, reduced absorption and CYP3A4 induction.


Subject(s)
HIV Infections , HIV Integrase Inhibitors , Drug Interactions , HIV Infections/drug therapy , HIV Integrase Inhibitors/therapeutic use , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Male , Oxazines , Pyridones , Valproic Acid/therapeutic use
14.
Clin Transl Oncol ; 22(6): 844-851, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31392645

ABSTRACT

BACKGROUND: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed "non-drugable" progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. METHODS: We conducted a study on "post-progression" (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), "switched therapies" or best supportive care only (BSC). RESULTS: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35-0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33-0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68-1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52-1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). CONCLUSION: Our study confirmed that in clinical practice, in case of "non-druggable" disease progression, maintaining osimertinib beyond progression (with adjunctive LATs) is an effective option.


Subject(s)
Acrylamides/therapeutic use , Aniline Compounds/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Combined Modality Therapy , Disease Progression , ErbB Receptors/antagonists & inhibitors , Female , Health Knowledge, Attitudes, Practice , Humans , Italy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Mutation , Survival Analysis , Treatment Outcome
15.
Chaos ; 29(8): 083110, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31472490

ABSTRACT

Realizing the behavior of the solution in the asymptotic situations is essential for repetitive applications in the control theory and modeling of the real-world systems. This study discusses a robust and definitive attitude to find the interval approximate asymptotic solutions of fractional differential equations (FDEs) with the Atangana-Baleanu (A-B) derivative. In fact, such critical tasks require to observe precisely the behavior of the noninterval case at first. In this regard, we initially shed light on the noninterval cases and analyze the behavior of the approximate asymptotic solutions, and then, we introduce the A-B derivative for FDEs under interval arithmetic and develop a new and reliable approximation approach for fractional interval differential equations with the interval A-B derivative to get the interval approximate asymptotic solutions. We exploit Laplace transforms to get the asymptotic approximate solution based on the interval asymptotic A-B fractional derivatives under interval arithmetic. The techniques developed here provide essential tools for finding interval approximation asymptotic solutions under interval fractional derivatives with nonsingular Mittag-Leffler kernels. Two cases arising in the real-world systems are modeled under interval notion and given to interpret the behavior of the interval approximate asymptotic solutions under different conditions as well as to validate this new approach. This study highlights the importance of the asymptotic solutions for FDEs regardless of interval or noninterval parameters.

16.
Pharmacogenomics J ; 19(1): 65-71, 2019 02.
Article in English | MEDLINE | ID: mdl-30405212

ABSTRACT

Tenofovir disoproxil fumarate (TDF) is a very effective antiviral drug that has been associated with tubular dysfunction. The aim of this study was to analyze the demographic, pharmacokinetic, and pharmacogenetic variables associated with TDF discontinuation for renal outcomes in stable HIV-positive patients using multivariable analyses. Three hundred and four patients were included (73% male, with median age and eCrCl of 45.3 years and 90.9 mL/min, respectively). After a median follow-up of 28.3 months, 27 patients discontinued TDF for renal adverse events [persistent urinary abnormalities (n = 21) or eCrCl < 60 mL/min (n = 6)] providing an incidence of 3.77 events per 100 patient-year. The probability of TDF discontinuation was higher with several features (male gender, older age, not Caucasians ancestry, absence of intravenous drug abuse, protease inhibitors, previous indinavir, HCV-positivity, lower CD4 cell count, detectable HIV-RNA, lower eCrCl, spot-urine proteinuria) and higher tenofovir concentrations but not genetic variants. Tenofovir plasma concentrations were prognostic of TDF discontinuation for renal adverse events suggesting that dose-adjustment may be warranted for long-term safety.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Kidney/drug effects , Protease Inhibitors/therapeutic use , Tenofovir/therapeutic use , Adult , CD4-Positive T-Lymphocytes/drug effects , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Precision Medicine/methods
17.
Epidemiol Infect ; 146(5): 612-618, 2018 04.
Article in English | MEDLINE | ID: mdl-29465024

ABSTRACT

Human papillomavirus (HPV) testing is used in the triage of women with a borderline smear result. The efficiency of testing women with a low-grade squamous intraepithelial lesion (LSIL) and atypical squamous cells of undetermined significance (ASCUS) is less clear. For this reason we used a new HPV test that detects E6/E7 messenger RNA (mRNA), which might have a higher specificity. The objective of this prospective study was to assess whether HPV E6/E7 mRNA positivity in women with ASCUS and LSIL at baseline, is able to predict those women who have a high risk of developing a histological cervical intraepithelial neoplasia (CIN2) or worse lesion. We took into consideration the women's age and HPV DNA genotype and followed them up for 3 years. Cervical samples from women with high-risk HPV (HR-HPV) DNA-positive ASCUS (n = 90) or LSIL (n = 222) were tested for the presence of HR-HPV E6/E7 mRNA and the women were monitored for the development of histopathologically verified CIN2+. Thirteen patients with ASCUS and 17 with LSIL did not complete follow-up. All patients with LSIL and ASCUS, enrolled in this study, had confirmed lesions at the colposcopic examination. Follow-up was available for 312 women, 193 were positive in the HR-HPV DNA test and 93 had a HPV E6/E7 mRNA positive test. Finally, 22 women positive in the HPV DNA test for high-risk genotypes and with positive E6/E7 mRNA had a histologically confirmed CIN2+. Only two cases with negative HPV E6/E7 mRNA had CIN2+. The study shows that women positive in the HPV E6/E7 mRNA test have a greater risk of malignant progression of cervical lesions and therefore deserve greater attention and earlier check-ups.


Subject(s)
Atypical Squamous Cells of the Cervix/classification , Oncogene Proteins, Viral/analysis , Papillomaviridae/isolation & purification , Squamous Intraepithelial Lesions of the Cervix/epidemiology , Uterine Cervical Dysplasia/epidemiology , Adolescent , Adult , Disease Progression , Female , Follow-Up Studies , Humans , Incidence , Italy/epidemiology , Middle Aged , Papanicolaou Test , Prevalence , Prospective Studies , RNA, Messenger/analysis , Squamous Intraepithelial Lesions of the Cervix/classification , Squamous Intraepithelial Lesions of the Cervix/etiology , Vaginal Smears , Young Adult , Uterine Cervical Dysplasia/etiology
18.
Oncogene ; 37(2): 231-240, 2018 01 11.
Article in English | MEDLINE | ID: mdl-28925395

ABSTRACT

Highly expressed in cancer protein 1 (Hec1) is a subunit of the kinetochore (KT)-associated Ndc80 complex, which ensures proper segregation of sister chromatids at mitosis by mediating the interaction between KTs and microtubules (MTs). HEC1 mRNA and protein are highly expressed in many malignancies as part of a signature of chromosome instability. These properties render Hec1 a promising molecular target for developing therapeutic drugs that exert their anticancer activities by producing massive chromosome aneuploidy. A virtual screening study aimed at identifying small molecules able to bind at the Hec1-MT interaction domain identified one positive hit compound and two analogs of the hit with high cytotoxic, pro-apoptotic and anti-mitotic activities. The most cytotoxic analog (SM15) was shown to produce chromosome segregation defects in cancer cells by inhibiting the correction of erroneous KT-MT interactions. Live cell imaging of treated cells demonstrated that mitotic arrest and segregation abnormalities lead to cell death through mitotic catastrophe and that cell death occurred also from interphase. Importantly, SM15 was shown to be more effective in inducing apoptotic cell death in cancer cells as compared to normal ones and effectively reduced tumor growth in a mouse xenograft model. Mechanistically, cold-induced MT depolymerization experiments demonstrated a hyper-stabilization of both mitotic and interphase MTs. Molecular dynamics simulations corroborate this finding by showing that SM15 can bind the MT surface independently from Hec1 and acts as a stabilizer of both MTs and KT-MT interactions. Overall, our studies represent a clear proof of principle that MT-Hec1-interacting compounds may represent novel powerful anticancer agents.


Subject(s)
Antineoplastic Agents/pharmacology , Microtubules/drug effects , Neoplasms/drug therapy , Nuclear Proteins/antagonists & inhibitors , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Chromosomal Instability/drug effects , Chromosomal Instability/genetics , Chromosome Segregation/drug effects , Computer Simulation , Cytoskeletal Proteins , Drug Screening Assays, Antitumor/methods , Humans , Inhibitory Concentration 50 , Interphase/drug effects , Kinetochores/metabolism , Male , Mice , Mice, Nude , Microtubules/metabolism , Mitosis/drug effects , Molecular Docking Simulation , Neoplasms/pathology , Nuclear Proteins/chemistry , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Protein Domains/drug effects , Xenograft Model Antitumor Assays
19.
Neurochirurgie ; 63(6): 473-477, 2017 Dec.
Article in French | MEDLINE | ID: mdl-29128087

ABSTRACT

The spine has been the subject of extensive clinical research since it is the source of many painful complaints. However, there is little scientific evidence concerning the therapeutic proposals. During the course of life, the intervertebral disc degenerates, which over time diminishes its damping capacity and facilitates the expulsion of the nucleus pulposus through the annulus fibrosus. The degeneration of the intervertebral disc (DDI) is the origin of some back pain and various specific treatments have been developed. These include the infiltration at the center of the intervertebral disc of plasma rich platelet (PRP), composed of multiple growth factors which act on the disc degeneration. This treatment is recent and less invasive than surgery. Preliminary results seem promising. However, many gray areas and several parameters remained to be clarified. In an attempt to do this, a literature review was conducted based on bibliographic databases Pubmed, Medline and Scopus® using the following Mesh terms : PRP, platelet-rich plasma, intradiscal disc degeneration, disc, intradiscal, discogenic. This analysis reveals that at the present time, no reported study has a sufficient perspective to judge the effectiveness of the infiltration of PRP. Early harvest results will be used to set the limits of this treatment. Accordingly, it is therefore currently recommended to introduce PRP injection as a complementary solution to comprehensive care of the spine. Future research will need to generate randomized controlled studies including comparing the results with conservative treatment and measure the cost-benefit relationship.


Subject(s)
Intervertebral Disc Degeneration/therapy , Platelet-Rich Plasma , Back Pain/etiology , Back Pain/therapy , Humans , Intervertebral Disc Degeneration/complications
20.
Clin Ter ; 168(4): e258-e261, 2017.
Article in English | MEDLINE | ID: mdl-28703841

ABSTRACT

OBJECTIVE: The aim of this study is to assess the reliability of the Adolescent Label Impact Index (ALII) , it is an adolescent adapted version of Italian LII of the tobacco products warnings. MATERIAL AND METHODS: A sample including students aged 13-15 years was considered. The ALII is constructed by 4 items: salience, harm, quitting and forgo. The questionnaire was self-administered to study participants twice with 3 days between each administration (T1 and T2) to measure reliability. The internal consistency using Cronbach's alpha and Corrected Item-Total Correlations (CITC) and the test-retest reliability applying Pearson's correlation were computed. RESULTS: Cronbach's alpha ranges from 0.625 at T1 to 0.715 at T2. The "salience" resulted the item with the lowest CITC value (=0.281). The Pearson's coefficient was r=0.909 (p<0.001). CONCLUSIONS: The instruments is low in cost and easy to administer and analyses in a setting people aged 13-15 years. The ALII shown an acceptable consistency and excellent stability over time. However, attention has to be paid when the ALII is administered to the no smoking teens and who has never seen the tobacco product labels to allow an appropriate interpretation of the data collected.


Subject(s)
Product Labeling , Tobacco Smoking , Adolescent , Female , Humans , Italy , Male , Psychometrics , Reproducibility of Results , Students , Surveys and Questionnaires
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