RESUMO
The objective of the study was to examine the impact of a multi-strain probiotic (MSP) on sleep, physical activity, and body composition changes. We used a randomised, double-blind, placebo-controlled approach with 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented daily with MSP (4 × 109 live cells Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04; Probiotical S.p.A., Novara, Italy) or placebo (PLA). In response to supplementation (after 0, 2, 4, and 6 weeks of supplementation) and 3 weeks after stopping supplementation, participants had subjective (Pittsburgh Sleep Quality Index, PSQI) and objective sleep indicators, body composition, daily physical activity and resting hemodynamics assessed. Subjective sleep quality indicators using the PSQI (sleep latency, sleep disturbance, and global PSQI score) improved ( P < 0.05) at various time points with MSP supplementation. Systolic blood pressure in PLA increased ( P < 0.05) after 6 weeks of supplementation with no change in MSP. No changes ( P > 0.05) in sleep (hours asleep, minutes awake, number of times awake) or physical activity (step count, minutes of sedentary activity, total active minutes) metrics assessed by the wearable device were observed. Additionally, no changes in resting heart rate, diastolic blood pressure, and body composition were discerned. In conclusion, MSP supplementation improved the subjective ability to fall asleep faster and disturbances experienced during sleep, which resulted in improved overall sleep quality as assessed by the PSQI. No differences in other sleep indicators, physical activity, hemodynamics, and body composition were observed during or following MSP supplementation. Registered at clinicaltrials.gov: NCT05343533.
Assuntos
Composição Corporal , Exercício Físico , Hemodinâmica , Probióticos , Qualidade do Sono , Humanos , Probióticos/administração & dosagem , Masculino , Feminino , Método Duplo-Cego , Adulto , Exercício Físico/fisiologia , Hemodinâmica/efeitos dos fármacos , Adulto Jovem , Suplementos Nutricionais , Lacticaseibacillus rhamnosus/fisiologiaRESUMO
BACKGROUND AND PURPOSE: Following the commercial availability of nusinersen, there have been a number of new referrals of adults with spinal muscular atrophy (SMA) not regularly followed in tertiary-care centers or enrolled in any disease registry. METHODS: We compared demographics and disease characteristics, including assessment of motor and respiratory function, in regularly followed patients and newcomers subdivided according to the SMA type. RESULTS: The cohort included 166 adult patients (mean age: 37.09 years): one type I, 65 type II, 99 type III, and one type IV. Of these 166, there were 67 newcomers. There was no significant difference between newcomers and regularly followed patients in relation to age and disease duration. The Hammersmith Functional Motor Scale Expanded and Revised Upper Limb Module scores were higher in the regularly followed patients compared to newcomers in the whole cohort and in both SMA II and II. A difference was also found on ventilatory status (p = 0.013) and Cobb's angle >50° (p = 0.039) between the two subgroups. No difference was found in scoliosis surgery prevalence (p > 0.05). CONCLUSIONS: Our results showed differences between the two subgroups, even if less marked in the type III patients. In the type II patients, there was a higher proportion of newcomers who were in the severe end of the spectrum. Of the newcomers, only approximately a third initiated treatment, as opposed to the 51% in the regularly followed patients. The identification of patients who were not part of the registries will help to redefine the overall prevalence of SMA and the occurrence of different phenotypes.
Assuntos
Atrofia Muscular Espinal , Atrofias Musculares Espinais da Infância , Adulto , Estudos de Coortes , Humanos , Atrofia Muscular Espinal/tratamento farmacológico , Atrofia Muscular Espinal/epidemiologia , Oligonucleotídeos , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Atrofias Musculares Espinais da Infância/epidemiologiaRESUMO
Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.
Assuntos
Oncologia/normas , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/terapia , Patologia Clínica/normas , Idoso , Consenso , Humanos , Oncologia/organização & administração , Pessoa de Meia-Idade , Patologia Clínica/organização & administração , Sociedades Médicas/organização & administração , Sociedades Médicas/normas , EspanhaRESUMO
BACKGROUND: Myosin heavy chain 7 (MYH7)-related myopathies are emerging as an important group of muscle diseases of childhood and adulthood, with variable clinical and histopathological expression depending on the type and location of the mutation. Mutations in the head and neck domains are a well-established cause of hypertrophic cardiomyopathy whereas mutation in the distal regions have been associated with a range of skeletal myopathies with or without cardiac involvement, including Laing distal myopathy and Myosin storage myopathy. Recently the spectrum of clinical phenotypes associated with mutations in MYH7 has increased, blurring this scheme and adding further phenotypes to the list. A broader disease spectrum could lead to misdiagnosis of different congenital myopathies, neurogenic atrophy and other neuromuscular conditions. RESULTS: As a result of a multicenter Italian study we collected clinical, histopathological and imaging data from a population of 21 cases from 15 families, carrying reported or novel mutations in MYH7. Patients displayed a variable phenotype including atypical pictures, as dropped head and bent spine, which cannot be classified in previously described groups. Half of the patients showed congenital or early infantile weakness with predominant distal weakness. Conversely, patients with later onset present prevalent proximal weakness. Seven patients were also affected by cardiomyopathy mostly in the form of non-compacted left ventricle. Muscle biopsy was consistent with minicores myopathy in numerous cases. Muscle MRI was meaningful in delineating a shared pattern of selective involvement of tibialis anterior muscles, with relative sparing of quadriceps. CONCLUSION: This work adds to the genotype-phenotype correlation of MYH7-relatedmyopathies confirming the complexity of the disorder.
Assuntos
Miosinas Cardíacas/metabolismo , Doenças Musculares/diagnóstico , Cadeias Pesadas de Miosina/metabolismo , Adolescente , Adulto , Idoso , Miosinas Cardíacas/genética , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Extremidade Inferior/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Doenças Musculares/patologia , Mutação/genética , Cadeias Pesadas de Miosina/genética , Linhagem , Fenótipo , Adulto JovemRESUMO
OBJECTIVE: To assess the clinical course and genotype-phenotype correlations in patients with selenoprotein-related myopathy (SEPN1-RM) due to selenoprotein N1 gene (SEPN1) mutations for a retrospective cross-sectional study. METHODS: Forty-one patients aged 1-60 years were included. Clinical data including scoliosis, respiratory function, and growth measurements were collected by case note review. RESULTS: Mean age at onset was 2.7 years, ranging from birth to the second decade of life. All but 2 remained independently ambulant: one lost ambulation at age 5 years and another in his late 50s. The mean age of starting nocturnal noninvasive ventilation (NIV) was 13.9 years. One child required full-time NIV at the age of 1 year while in 2 cases NIV was started at 33 years. Two patients died from respiratory failure at the age of 10 and 22 years, respectively. The mean age at scoliosis onset was 10 years, in most cases preceded by rigidity of the spine. Fourteen patients had successful spinal surgery (mean age 13.9 years). Twenty-one were underweight; however, overt feeding difficulties were not a feature. CONCLUSIONS: This study describes the largest population affected by SEPN1-RM reported so far. Our findings show that the spectrum of severity is wider than previously reported. Respiratory insufficiency generally develops by 14 years but may occur as early as in infancy or not until the fourth decade. Motor abilities remain essentially static over time even in patients with early presentation. Most adult patients remain ambulant and fully employed.
Assuntos
Estudos de Associação Genética , Proteínas Musculares/genética , Doenças Musculares/genética , Doenças Musculares/fisiopatologia , Selenoproteínas/genética , Índice de Gravidade de Doença , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Doenças Musculares/patologia , Mutação , Adulto JovemRESUMO
BACKGROUND: Cognitive impairment has been reported in a significant proportion of patients with congenital muscular dystrophies (CMD), generally associated with brain changes. OBJECTIVES: The aim of this study was to establish 1) the overall prevalence of CMD and cognitive impairment in the Italian population; 2) the frequency of individual genetically defined forms; and 3) the presence of distinct phenotypes not associated with mutations in the known genes. METHODS: We included all patients with CMD and cognitive impairment followed in all the Italian tertiary neuromuscular centers. Clinical, brain MRI, and morphologic data were collected. Genetic screening of the known genes was performed according to clinical and muscle biopsy findings. RESULTS: Ninety-two of the 160 (58%) patients with CMD followed in our centers had cognitive impairment. alpha-Dystroglycan (alpha-DG) reduction on muscle biopsy was found in 73/92 (79%), with 42/73 carrying mutations in the known genes. Another 6/92 (7%) showed a laminin alpha2 deficiency on muscle biopsy and 5 of the 6 carried mutations in LAMA2. The remaining 13/92 (14%) patients had normal alpha-DG and laminin alpha2 expression on muscle. CONCLUSIONS: This is the first population study establishing the prevalence of CMD and cognitive impairment and providing a classification on the basis of clinical, MRI, and genetic findings. We also showed that cognitive impairment was not always associated with alpha-DG or laminin alpha2 reduction or with structural brain changes.
Assuntos
Encéfalo/patologia , Transtornos Cognitivos/epidemiologia , Distrofias Musculares/congênito , Distrofias Musculares/epidemiologia , Mapeamento Encefálico , Transtornos Cognitivos/genética , Transtornos Cognitivos/patologia , Comorbidade , Distroglicanas/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Processamento de Imagem Assistida por Computador , Itália/epidemiologia , Laminina/genética , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético/patologia , Distrofias Musculares/genética , Distrofias Musculares/patologia , Mutação , Fenótipo , PrevalênciaRESUMO
BACKGROUND: Congenital muscular dystrophies (CMD) with reduced glycosylation of alpha-dystroglycan (alpha-DG) are a heterogeneous group of conditions associated with mutations in six genes encoding proven or putative glycosyltransferases. OBJECTIVES: The aim of the study was to establish the prevalence of mutations in the six genes in the Italian population and the spectrum of clinical and brain MRI findings. METHODS: As part of a multicentric study involving all the tertiary neuromuscular centers in Italy, FKRP, POMT1, POMT2, POMGnT1, fukutin, and LARGE were screened in 81 patients with CMD and alpha-DG reduction on muscle biopsy (n = 76) or with a phenotype suggestive of alpha-dystroglycanopathy but in whom a muscle biopsy was not available for alpha-DG immunostaining (n = 5). RESULTS: Homozygous and compound heterozygous mutations were detected in a total of 43/81 patients (53%), and included seven novel variants. Mutations in POMT1 were the most prevalent in our cohort (21%), followed by POMT2 (11%), POMGnT1 (10%), and FKRP (9%). One patient carried two heterozygous mutations in fukutin and one case harbored a new homozygous variant in LARGE. No clear-cut genotype-phenotype correlation could be observed with each gene, resulting in a wide spectrum of clinical phenotypes. The more severe phenotypes, however, appeared to be consistently associated with mutations predicted to result in a severe disruption of the respective genes. CONCLUSIONS: Our data broaden the clinical spectrum associated with mutations in glycosyltransferases and provide data on their prevalence in the Italian population.
Assuntos
Distroglicanas/metabolismo , Glicosiltransferases/genética , Distrofias Musculares/congênito , Distrofias Musculares/genética , Adolescente , Encéfalo/patologia , Criança , Pré-Escolar , Estudos de Coortes , Distroglicanas/análise , Feminino , Glicosilação , Humanos , Lactente , Itália , Imageamento por Ressonância Magnética , Manosiltransferases/genética , Proteínas de Membrana/genética , Músculo Esquelético/química , Músculo Esquelético/patologia , Distrofias Musculares/metabolismo , Distrofias Musculares/patologia , Mutação , N-Acetilglucosaminiltransferases/genética , Pentosiltransferases , Fenótipo , Prevalência , Proteínas/genéticaRESUMO
Mutations in POMT1 and POMT2 genes were originally identified in Walker-Warburg syndrome (WWS) and subsequently reported in patients with milder phenotypes characterised by mental retardation with or without brain abnormalities and without ocular malformations. As part of a multicentric Italian study we screened the POMT1 and POMT2 genes in 61 congenital muscular dystrophy (CMD) patients with alpha-dystroglycan reduction on muscle biopsy and/or clinical and radiological findings suggestive of the known forms of CMD with alpha-dystroglycan deficiency. The aim of the study was to establish how frequently mutations in POMT1 and POMT2 occur in CMD patients in the Italian population and to evaluate the spectrum of associated phenotypes. Thirteen patients showed mutations in POMT1 and five harboured mutations in POMT2, accounting for a total of 20 different mutations, eight of which were novel (two in POMT1 and six in POMT2). Normal brain MRI associated with mental retardation and microcephaly was the most frequent finding in patients with mutations in POMT1 (six out of 13), but was also found in a patient with POMT2 mutations. Predominant cerebellar hypoplasia was also frequent both in patients with POMT1 (three out of 13) and POMT2 (three out of 5) mutations. A MEB phenotype with frontal cortical dysplasia and pons abnormalities was found in two patients with POMT1 and in one with POMT2 mutations, while a WWS phenotype was only found in a case with mutations in POMT1. Mutations causing frameshifts and stop codons were responsible for the more severe phenotypes. Our results provide further evidence that, as previously reported for FKRP, the array of mutations in POMT1 and POMT2 is ample and the spectrum of associated phenotypes is wider than initially thought.
Assuntos
Saúde da Família , Manosiltransferases/genética , Distrofias Musculares/genética , Mutação , Adolescente , Adulto , Encefalopatias/genética , Encefalopatias/patologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Distroglicanas/metabolismo , Feminino , Humanos , Itália , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofias Musculares/patologia , FenótipoRESUMO
The Hammersmith Infant Neurological Examination was performed in 24 infants with cystic periventricular leukomalacia whose gestational age ranged between 26-38 weeks. The infants were examined between 6 and 9.5 months corrected age. The aim of the study was to establish the different patterns of neurological abnormality as well as the optimality scores that predict the severity of motor sequelae at 2 years. Increased neck and trunk extensor tone, and a posture of flexed arms and extended legs between 6 and 9 months were always associated with the inability to sit unsupported at 2 years, whilst truncal hypotonia and extended arms and legs were associated with unsupported sitting but not walking. Optimality scores between 41 and 60 were generally associated with sitting but not walking at 2 years whilst scores below 40 were always associated with the inability to sit independently at 2 years. All infants who did not develop cerebral palsy at 2 years had scores > 60. Our results suggest that the pattern of findings on neurological examination performed between 6 and 9 months as well as the calculated optimality score helps to predict motor impairment in infants with PVL.
Assuntos
Leucomalácia Periventricular/diagnóstico , Leucomalácia Periventricular/fisiopatologia , Exame Neurológico/métodos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Atividade Motora/fisiologia , Avaliação de Resultados em Cuidados de Saúde , Ultrassonografia/métodosRESUMO
The aim of this study was to assess various aspects of visual function in 6 patients (age range: 9 months to 7 years and 8 months) with methylmalonic aciduria and homocystinuria. All patients had an ophthalmological examination and were tested with a battery of age-appropriate tests assessing various aspects of visual function such as acuity, visual fields and visual attention. None of the patients had significant retinal abnormalities but all 6 had nystagmus which was associated with strabismus in 3 of the 6. They all had some abnormalities on the behavioral tests assessing visual function which appeared to be related to the age of the patients. Visual impairment was more severe in the 3 patients below 3 years of age and milder in the older patients. The presence and the severity of abnormalities, in contrast, did not depend on the age at onset or the age when treatment was started and were only partly related to brain MRI findings. Severe hydrocephalus and basal ganglia involvement were associated with severe visual impairment, but abnormal visual findings were also present in the children with normal MRI and isolated mild periventricular changes. Our results suggest that age, brain lesions and other factors may be responsible for visual abnormalities in methylmalonic aciduria and homocystinuria. Further studies using early and sequential assessment of visual function are needed to establish whether the differences observed between younger and older children may be related to the duration of therapy.
Assuntos
Homocistinúria/fisiopatologia , Ácido Metilmalônico/urina , Visão Ocular/fisiologia , Atenção/fisiologia , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Cognição/fisiologia , Homocistinúria/psicologia , Humanos , Lactente , Atividade Motora/fisiologia , Músculos Oculomotores/fisiopatologia , Nervo Oculomotor/fisiopatologia , Retina/patologia , Retina/fisiopatologia , Disparidade Visual/fisiologiaRESUMO
We describe 2 cases of Goldenhar syndrome with severe abnormalities of the pons. The first case is a 10-month-old Caucasian female infant. At birth the girl showed polydactyly, labiopalatoschisis, right ear agenesis, left eye coloboma and vertebral anomalies. She also had marked hypotonia, severely reduced movements and respiratory and feeding abnormalities. She required gastrostomy at 5 months and tracheostomy at 7 months. Brain MRI scans showed moderate cerebellar hypoplasia and severe abnormalities of the pons with a congenital cleft. The child died at age 12 months. Case 2 is a Caucasian boy. Clinical signs and presentation were similar to case 1. The child also had severely reduced lacrimation, sweating, with thermoregulation abnormalities. He also underwent gastrostomy at 18 months. The child is now 3 years old and is able to sit only with support. Brain MRI was similar to case 1. The association of Goldenhar syndrome and pons abnormalities in 2 subjects suggests that this is more than a mere coincidence. Further studies and characterization of the genes involved in Goldenhar syndrome are needed to establish an adequate genotype-phenotype correlation.