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M Luciano

Publications and source records attributed to M Luciano.

At least 19 recordsLinked to original sources
PubMed2025

Multi-Polygenic prediction of Frailty and its Trajectories highlights Chronic Pain, Rheumatoid Arthritis, and Educational Attainment pathways.

Frailty is a complex ageing-related trait with a growing evidence base for genetic influence. While a single polygenic score (PGS) for frailty has shown predictive value, few studies have examined the joint effect of multiple genetic risks. This study used a multi-polygenic score (MPS) approach to evaluate the combined and relative contributions of 26 PGSs to frailty, measured via the Frailty Index (FI), in two UK cohorts aged 65 and older: the English Longitudinal Study of Ageing (ELSA) and the Lothian Birth Cohort 1936 (LBC1936). Using elastic net regression with repeated cross-validation, we identified chronic pain and depressive symptoms PGSs as the strongest risk predictors of cross-sectional frailty status, while educational attainment, parental longevity, and rheumatoid arthritis PGSs were protective. Compared to single PGS models, MPS models provided improved prediction of frailty levels, explaining up to 4.7% of variance in frailty status - an improvement over the best single PGS (2.5%). To assess whether PGSs also predicted longitudinal frailty progression, we applied generalized additive mixed models (GAMMs) to model age-related trajectories. In ELSA, five PGSs (chronic pain, depressive symptoms, rheumatoid arthritis, educational attainment, and parental death) significantly interacted with age, influencing the rate of frailty change. In LBC1936, consistent though weaker effects were observed for chronic pain and education PGSs. These findings show that polygenic liability shapes both frailty levels and trajectories in later life. Our results support the use of multi-trait genomic models to improve risk prediction and understanding of frailty's complex aetiology.

Journal Article↗
PubMed2007

Effects of SCA1, MJD, and DPRLA triplet repeat polymorphisms on cognitive phenotypes in a normal population of adolescent twins.

The expansion of unstable trinucleotide CAG repeat polymorphisms of a number of genes causes several neurodegenerative disorders with decreased cognitive function, the severity of the disorder being related to allele length at the triplet repeat locus. While the effects of repeat length have been well studied in clinical samples, there has been little investigation of the effects of triplet repeat variation in the normal range for these genes. We have, therefore, examined linkage and association for three CAG triplet repeat markers (Spinocerebellar Ataxia Type 1, SCA1; Machado-Joseph Disease, MJD; Dentatorubro-pallidoluysian Atrophy, DRPLA) to assess their contribution to variation in cognitive ability (IQ, reading ability, processing speed) in a normal, unselected sample of adolescent twins (248 dizygotic (DZ) sibling pairs, aged 16 years). Association tests, performed in Mx and QTDT, showed a consistent positive association of SCA1 with Arithmetic (P = 0.04). While association was supported between SCA1 and Cambridge reading scores and between DRPLA and inspection time, results were inconsistent across software packages. Given the number of statistical tests performed, it is unlikely that trinucleotide repeat variation in the normal range for these genes influences variation in normal cognition.

Adolescent↗
PubMed2006

Effect of the BDNF V166M polymorphism on working memory in healthy adolescents.

Brain-derived neurotrophic factor (BDNF) may play a role in modulating memory function and there is growing evidence that the BDNF V166M polymorphism may influence episodic memory in humans. However, previous association studies examining this polymorphism and working memory are inconsistent. The current study examined this association in a large sample of adolescent twin-pairs and siblings (785 individuals from 439 families). A range of measures (event-related potential, general performance and reaction time) was obtained from a delayed-response working-memory task and total association was examined using the quantitative transmission disequilibrium tests (QTDT) program. Analyses had approximately 93-97% power (alpha= 0.05) to detect an association accounting for as little as 2% of the variance in the phenotypes examined. Results indicated that the BDNF V166M polymorphism is not associated with variation in working memory in healthy adolescents.

Adolescent↗
PubMed2005

Genome-wide scan of IQ finds significant linkage to a quantitative trait locus on 2q.

A genome-wide linkage scan of 795 microsatellite markers (761 autosomal, 34 X chromosome) was performed on Multidimensional Aptitude Battery subtests and verbal, performance and full scale scores, the WAIS-R Digit Symbol subtest, and two word-recognition tests (Schonell Graded Word Reading Test, Cambridge Contextual Reading Test) highly predictive of IQ. The sample included 361 families comprising 2-5 siblings who ranged in age from 15.7 to 22.2 years; genotype, but not phenotype, data were available for 81% of parents. A variance components analysis which controlled for age and sex effects showed significant linkage for the Cambridge reading test and performance IQ to the same region on chromosome 2, with respective LOD scores of 4.15 and 3.68. Suggestive linkage (LOD score>2.2) for various measures was further supported on chromosomes 6, 7, 11, 14, 21 and 22. Where location of linkage peaks converged for IQ subtests within the same scale, the overall scale score provided increased evidence for linkage to that region over any individual subtest. Association studies of candidate genes, particularly those involved in neural transmission and development, will be directed to genes located under the linkage peaks identified in this study.

Chromosome Mapping↗
PubMed2005

Genetic covariation between event-related potential (ERP) and behavioral non-ERP measures of working-memory, processing speed, and IQ.

The aim of this study was to identify genetic covariants for fundamental measures of brain function (event-related potentials (ERPs): P300 latency and slow wave amplitude recorded in a working-memory task) and more complex cognitive measures (behavioral non-ERP measures: working-memory performance, information processing speed, IQ). Data were collected from 252 monozygotic and 297 dizygotic twin pairs aged 16. Multivariate modeling identified two independent genetic factors associated with processing speed that also influenced working-memory performance (one reflected the duration of neural activity required to evaluate target information, the other reflected more general cognitive and speed-related abilities). However, the allocation of neural resources, as assessed by ERP slow wave amplitude measures, was not associated with the other cognitive measures investigated. Thus, of the ERP measures examined, P300 latency, but not slow wave amplitude, may be an informative measure to include (i.e., with working-memory performance) in future multivariate linkage and association analyses of cognitive function.

Cognition↗
PubMed2001

Genetic covariance among measures of information processing speed, working memory, and IQ.

The genetic relationship between lower (information processing speed), intermediate (working memory), and higher levels (complex cognitive processes as indexed by IQ) of mental ability was studied in a classical twin design comprising 166 monozygotic and 190 dizygotic twin pairs. Processing speed was measured by a choice reaction time (RT) task (2-, 4-, and 8-choice), working memory by a visual-spatial delayed response task, and IQ by the Multidimensional Aptitude Battery. Multivariate analysis, adjusted for test-retest reliability, showed the presence of a genetic factor influencing all variables and a genetic factor influencing 4- and 8-choice RTs, working memory, and IQ. There were also genetic factors specific to 8-choice RT, working memory, and IQ. The results confirmed a strong relationship between choice RT and IQ (phenotypic correlations: -0.31 to -0.53 in females, -0.32 to -0.56 in males; genotypic correlations: -0.45 to -0.70) and a weaker but significant association between working memory and IQ (phenotypic: 0.26 in females, 0.13 in males; genotypic: 0.34). A significant part of the genetic variance (43%) in IQ was not related to either choice RT or delayed response performance, and may represent higher order cognitive processes.

Adolescent↗
PubMed2001

Genetics of cognition: outline of a collaborative twin study.

A multidisciplinary collaborative study examining cognition in a large sample of twins is outlined. A common experimental protocol and design is used in The Netherlands, Australia and Japan to measure cognitive ability using traditional IQ measures (i.e., psychometric IQ), processing speed (e.g., reaction time [RT] and inspection time [IT]), and working memory (e.g., spatial span, delayed response [DR] performance). The main aim is to investigate the genetic covariation among these cognitive phenotypes in order to use the correlated biological markers in future linkage and association analyses to detect quantitative-trait loci (QTLs). We outline the study and methodology, and report results from our preliminary analyses that examines the heritability of processing speed and working memory indices, and their phenotypic correlation with IQ. Heritability of Full Scale IQ was 87% in the Netherlands, 83% in Australia, and 71% in Japan. Heritability estimates for processing speed and working memory indices ranged from 33-64%. Associations of IQ with RT and IT (-0.28 to -0.36) replicated previous findings with those of higher cognitive ability showing faster speed of processing. Similarly, significant correlations were indicated between IQ and the spatial span working memory task (storage [0.31], executive processing [0.37]) and the DR working memory task (0.25), with those of higher cognitive ability showing better memory performance. These analyses establish the heritability of the processing speed and working memory measures to be used in our collaborative twin study of cognition, and support the findings that individual differences in processing speed and working memory may underlie individual differences in psychometric IQ.

Adolescent↗
PubMed2000

Sex differences in the perception of tactile simultaneity.

A tactile simultaneity task was used to investigate the effects of sex on simultaneity thresholds. Participants were required to judge whether pairs of tactile stimuli delivered unimanually or bimanually were simultaneous. Unimanual stimulation delivered stimuli to the same cerebral hemisphere, while bimanual stimulation resulted in the delivery of one stimulus to each hemisphere, therefore requiring interhemispheric transmission before judging simultaneity. The data of 114 right-handed participants were analysed. Females (N = 56) perceived simultaneity at longer intervals than males (N = 58) when bimanual stimulation was received. Furthermore, males had shorter interhemispheric transmission times (10.9 ms) than those of females (15.0 ms). The results also provided some support for the predictions of the Hemispheric Equivalence Model of temporal processing since bimanual simultaneity thresholds were longer than unimanual; and unimanual stimulation of the left vs right hand did not differ. An advantage for stimulation of right hand first (vs left first) in the bimanual condition was small (2.7 ms), and was the only prediction of the Left Hemisphere Specialisation Model to receive support. A modification of the Equivalence Model which allows for a slight left hemispheric advantage is proposed.

Adolescent↗
PubMed2000

Effects of preferred hand and sex on the perception of tactile simultaneity.

The effects of handedness, sex and the influence of hand placement in extrapersonal space on temporal information processing was investigated by measuring thresholds for perceiving the simultaneity of pairs of tactile stimuli. Simultaneity thresholds of preferred right handed and left handed university students with left hemisphere speech representation were compared using unimanual and bimanual stimulation at three hand placements (midline, lateral and crossed). In unimanual conditions two fingers of one hand were stimulated (single hemisphere), whereas in the bimanual conditions one finger of each hand was stimulated (cross hemispheres). Bimanual minus unimanual thresholds provided an estimate of interhemisphere transmission time (IHTT) regardless of hand placement. The effects of hemispace varied with the type of stimulation. With unimanual stimulation, overall thresholds were longer at the midline placement, however, with bimanual stimulation, thresholds were longer when the hands were spatially separated (crossed and/or uncrossed). Left handers' IHTTs were 8 ms faster than those of right handers. IHTTs in males were faster than females with hands placed in lateral (by 10.8 ms) or crossed (by 9.8 ms) but not midline positions. It was concluded that the cerebral hemispheres are equally capable of discriminating temporal intervals, but that the left hemisphere predominates when there is uncertainty about location of stimulation.

Adolescent↗
PubMed1999

Incidence and management of subdural hematoma/hygroma with variable- and fixed-pressure differential valves: a randomized, controlled study of programmable compared with conventional valves.

Shunt systems with differential pressure valves are prone to the complications of overdrainage. A programmable valve permits adjustment of the opening pressure of the valve. In this paper the authors report the incidence of subdural fluid collections in a randomized trial of programmable compared with conventional valves, and they describe methodologies used in management of this complication. A multiinstitutional, prospective, randomized trial of the Codman Hakim programmable valve and conventional fixed-pressure valves was undertaken. Two classes were defined: "new" and "replacement" valves. Randomization of the type of valve in each group was performed at each study site. Clinical and radiological studies were required at fixed intervals over a 104-week period. All complications were reported. The experimental valves were required to be reprogrammed after magnetic resonance imaging studies, but all other decisions regarding pressure setting were left to each investigator. Three hundred seventy-seven patients were randomized; 194 were treated with a programmable valve and 183 with a fixed-pressure valve. The two groups were statistically similar in demographic composition, as were the "new" and "replacement" categories. The investigators made 540 valve pressure changes (five per patient; range one-41 changes). More than half of the reprogramming adjustments were made in the first 3 months postplacement; 70% were made within 6 months. More than half of all reprogramming adjustments were required in a group of 30 patients. Four treatment modalities were observed: 1) 30% of the fluid collections resolved spontaneously (25% in the patients with programmable valves and 36.3% in those with conventional valves) and were largely found to be hygromas in infants and children; 2) four subdural fluid collections were unresolved and under observation; 3) the subdural hematoma was drained and the shunt removed (in 8.3% of patients with the programmable valve and 36.3% of those with the control valve); 4) the pressure of programmable valve was raised in 58% of patients (seven of 12), and this increase in opening pressure was a feature used by investigators to affect treatment. There was no significant difference in the incidence of subdural fluid collections between the programmable and fixed-pressure valve treatment groups. The programmable feature provided a considerable advantage in treatment when subdural collections occurred.

Journal Article↗
PubMed1999

[Interstitial cystitis: epidemiology].

The epidemiological assessment of intestitial cystitis (IC) is not definitive as no diagnostic criteria, such as endoscopy or biochemical and anatomopathological examination, exist. The diagnosis is solely based on symptoms like urgency, frequency and pelvic pain. The first studies on the population date back from 20 years ago and show a percentage of 10 cases every 100 thousand inhabitants. There is weak link between genetic factors, immunological diseases, previous cystitis or eating habits and intestitial cystitis. Epidemiological studies have highlight the frequency of this disease, and stressed the importance of stricted behavioural rules for the first stages of intestitial cystitis.

Cystitis, Interstitial↗
PubMed1999

[Interstitial cystitis: surgical treatment].

Surgical therapy of interstitial cystitis must never be considered a first option but must be reserved for cases, less than 10%, in which conservative therapy has proven ineffectual. Surgical therapy includes a variety that started at the turn of the century. Neurosurgical denervation and perivesical denervation like cysto-cystoplasty and cystolysis, manipulate the innervation to reduce the bladder's hypersensitivity. This surgical approach may be considered in patients in whom bladder capacity is normal. The results are uncertain and the complications like neurogenic bladder relevant. Enterocystoplasty is much more widespread because interstitial cystitis is a benign disease that rarely required radical surgery. Augmentation cystoplasty and substitution cystoplasty are two variants but only the later has a rationale as it involves the resection of the detrusor which is the source of the pain. Detubularization drastically reduced urinary incontinence. The resection of the detrusor can be supratrigonal, subtrigonal or at the proximal urethra like in the orthotopic neobladder. If urinary diversion is chosen, the bladder must be removed. Before recommending surgical therapy each patient should undergo tests for the localization of the pain; moreover psychological and gynaecological evaluations should be made. If the bladder capacity exceeds 400 cc surgical operation is not advisable. If, on the other hand, the bladder capacity is lower than 400 cc substitution cystoplasty is first choice. If the patient suffers from trigonal cystitis or urethral hypersensitivity, urinary diversion is a better therapy. According to the questionnaires send to the Urologic Departments in Lombardy in 1998, the most widespread type of operation seems to be supratrigonal cystectomy + enterocystoplasty and augmentation cystoplasty. Subtrigonal cystectomy or urinary diversion are only occasionally chosen; continent pouch is the least frequent therapy at all.

Adult↗
PubMed1998

The microdissection cautery needle versus the cold scalpel in bicoronal incisions.

Craniofacial procedures commonly use scalp incisions to optimize surgical access and aesthetic results. Although the use of traditional electrocautery instruments on hair-bearing tissue has been limited secondary to the width of resulting alopecia, needle-tipped electrocautery devices with decreased energy transmission have been developed. This study investigates the cosmetic effect of such instruments on scalp incisions. Twelve children undergoing craniosynostotic correction via bicoronal incisions were included. One side of the incision was completed with the cold scalpel whereas the contralateral portion was effected using the Colorado MicroDissection Needle (Colorado Biomedical Inc., Evergreen, CO, U.S.A.) according to optimal usage instructions. At the conclusion of the study period, precise measurements of the resultant width of alopecia were obtained from the parietal and temporal regions bilaterally, and were analyzed statistically. Also, parents completed a questionnaire concerning subjective observations of the surgical incision and its healing. The portions of the incision completed with the Colorado MicroDissection Needle demonstrated a wider area of peri-incisional alopecia (5.8 +/- 1.8 mm) than that produced by the cold scalpel (3.5 +/- 0.87 mm). Not only was this increased width significant statistically (P < 0.05), in addition the disparity was noted by the majority of parents (10 of 12) either on the patient questionnaire or with nonsuggestive verbal questioning. The benefit of the hemostatic incisional technique of electrocautery with even needle-tipped instruments must be weighed carefully against its cosmetic consequences.

Alopecia↗
PubMed1998

Systemic T cell adoptive immunotherapy of malignant gliomas.

OBJECT: To determine the feasibility, toxicity, and potential therapeutic benefits of systemic adoptive immunotherapy, 10 patients with progressive primary or recurrent malignant glioma received this treatment. Adoptive immunotherapy, the transfer of immune T lymphocytes, is capable of mediating the regression of experimental brain tumors in animal models. In animal models, lymph nodes (LNs) that drain the tumor vaccine site are a rich source of tumor-immune T cells. METHODS: In this clinical study, patients were inoculated intradermally with irradiated autologous tumor cells and granulocyte macrophage-colony stimulating factor as an adjuvant. Cells from draining inguinal LNs, surgically resected 7 days after vaccination, were stimulated sequentially with staphylococcal enterotoxin A and anti-CD3, and a low dose of interleukin-2 (60 IU/ml) was used to expand the stimulated cells. The maximum cell proliferation was 350-fold over 10 days of culture. The activated cells were virtually all T cells consisting of various proportions of CD4 and CD8 cells. These cells were given to patients by intravenous infusion at doses ranging from 9 x 10(8) to 1.5 x 10(11). There were no Grade 3 or 4 toxicities associated with the treatment. Following T-cell transfer therapy, radiographic regression that lasted at least 6 months was demonstrated in two patients with recurrent tumors. One patient demonstrated stable disease that has lasted for more than 17 months. The remaining patients had progressive disease; however, four of the eight patients with recurrent tumor remain alive more than 1 year after surgery for recurrence. Three patients required intervention with corticosteroid agents or additional surgery approximately 1 month following cell transfer. CONCLUSIONS: These intriguing clinical observations warrant further trials to determine whether this approach can provide therapeutic benefits and improve survival.

Adjuvants, Immunologic↗
PubMed1997

Transnasal transseptal endoscopic approach to the sphenoid sinus.

A modified transseptal approach to the sphenoid sinus and pituitary gland utilizing rigid endoscopy has been developed by the Departments of Otolaryngology, Plastic Surgery, and Neurosurgery at The Cleveland Clinic Foundation. When compared with alternate approaches or the nonendoscopic transseptal procedure, the modified approach provides better visualization and increased illumination of the surgical sites. Other advantages include a decrease in operating time, dissection, bleeding, and postoperative morbidity without compromising nasal function in the postoperative period.

Adenoma↗
PubMed1997

Endoscopic approach for benign tumor ablation of the forehead and brow.

Resection of benign tumors of the forehead and brow raises aesthetic concerns. An endoscopic subperiosteal approach to benign bony and soft-tissue tumors in the supraorbital and frontotemporal regions permits extirpation of these masses without producing visible facial scars. Therefore, this technique was used for tumor resection in 4 patients. This procedure demonstrated magnified visualization of the masses, and safe access for excisional biopsy and bony contouring. In addition to more acceptable surgical scars, patients experienced no significant postoperative morbidity and a reduced incidence of swelling, discomfort, and scalp anesthesia. Therefore, we conclude that the endoscopic subperiosteal approach is a favorable alternative for resection of suitable tumors.

Adult↗
PubMed1996

[T1G3 bladder tumors: 5 years later].

We have evaluated 79 patients affected by bladder cancer T1G3: 31 underwent just endoscopy, 11 radiotherapy, 10 cystectomy and 27 topical chemotherapy. At five years 44 patients were alive and disease free, 7 were alive but recurrent in TA, 3 were alive but in metastatic progression, 17 were died because of the tumor, 3 died because of the therapy, and 5 died disease free. The authors believe that this patients could be treated with BCG as first treatment choice performing cystectomy when relapse or progression occuring.

Antibiotics, Antineoplastic↗