Prone positioning improves oxygenation in adult respiratory distress syndrome. This procedure has been widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. ...However, this procedure can also be responsible for nerve damage and plexopathy.
We retrospectively reviewed a series of 7 infectious patients with coronavirus disease 2019 who underwent prone positioning ventilation at the San Raffaele Hospital of Milan, Italy, during the SARS-CoV-2 pandemic.
Clinical and neurophysiological data of 7 patients with nerve compression injuries have been reported.
Health care workers should take into consideration the risk factors for prone positioning-related plexopathy and nerve damage, especially in patients with coronavirus disease 2019, to prevent this type of complication.
Abstract Several dominant mutations of CACNA1A gene were associated with at least three different allelic disorders: spino-cerebellar ataxia type 6 (SCA6), episodic ataxia type 2 (EA2), and familial ...hemiplegic migraine-1 (FHM1). It is generally thought that loss-of-function mutations are associated with EA2, gain-of-function missense mutations with FHM1, and abnormal CAG expansions with SCA6. But, overlapping features, atypical symptoms and co-occurrence of distinct phenotypes within the same family were reported. We describe a four generation family showing different phenotypes ranging from EA2 to SCA6 and carrying the p.D302N CACNA1A gene mutation. In our family the phenotypes maintained separate and gender differences corresponding to different phenotypes were observed.
Transthyretin (TTR) amyloidosis is a hereditary disease with a complex genotype-phenotype correlation. We conducted a literature survey to define the clinical landscape of TTR amyloidosis across ...populations worldwide. Then, we investigated whether the genetically determined TTR expression differs among human populations, contributing to the differences observed in patients. Polygenic scores for genetically determined TTR expression in 14 clinically relevant tissues were constructed using data from the GTEx (Genotype-Tissue Expression) project and tested in the samples from the 1,000 Genomes Project.
We observed differences among the ancestral groups and, to a lesser extent, among the investigated populations within the ancestry groups. Scandinavian populations differed in their genetically determined TTR expression of skeletal muscle tissue with respect to Southern Europeans (p = 6.79*10
). This is in line with epidemiological data related to Swedish and Portuguese TTR Val30Met endemic areas. Familial amyloidotic cardiomyopathy (TTR deposits occur primarily in heart tissues) presents clinical variability among human populations, a finding that agrees with the among-ancestry diversity of genetically determined TTR expression in heart tissues (i.e., Atrial Appendage p = 4.55*10
; Left Ventricle p = 6.54*10
).
Genetically determined TTR expression varied across human populations. This might contribute to the genotype-phenotype correlation of TTR amyloidosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Constipation is frequent amongst infants who have undergone surgery for anorectal malformation (ARM). Faecal retention, due to a dysfunctional enteric reflex of defaecation, can cause abdominal ...cramps, pseudoincontinence and, in the worst cases, megacolon. Prokinetic protocols are used to stimulate at least 1 bowel movement per day, including laxatives, enema, stools softeners and dietary schedules. While osteopathic manipulative treatment is adopted in adults for functional constipation, it has not been described for infants. Herein, we report the case of an infant undergoing anorectoplasty for a low ARM who was referred to the osteopath 2 years after the onset of severe constipation associated with pseudoincontinence and abdominal cramps and was refractory to the prokinetic protocol. In a child with a good ARM prognosis, autonomous daily bowel movements should be achieved. In this child, the imbalanced tension of the pelvic floor and immaturity of the parasympathetic plexus led to a functional alteration of the defaecation reflex. After adjunction of osteopathic manipulative treatment (OMT) to the therapeutic panel, the constipation showed gradual remission, with acquisition of autonomous defaecation 4 months after the therapy began. This suggests the importance of investigating the efficacy of OMT inclusion in the postsurgical prokinetic protocols for ARM patients with a good prognosis.
Coding mutations in TTR gene cause a rare hereditary form of systemic amyloidosis, which has a complex genotype-phenotype correlation. We investigated the role of non-coding variants in regulating ...TTR gene expression and consequently amyloidosis symptoms. We evaluated the genotype-phenotype correlation considering the clinical information of 129 Italian patients with TTR amyloidosis. Then, we conducted a re-sequencing of TTR gene to investigate how non-coding variants affect TTR expression and, consequently, phenotypic presentation in carriers of amyloidogenic mutations. Polygenic scores for genetically determined TTR expression were constructed using data from our re-sequencing analysis and the GTEx (Genotype-Tissue Expression) project. We confirmed a strong phenotypic heterogeneity across coding mutations causing TTR amyloidosis. Considering the effects of non-coding variants on TTR expression, we identified three patient clusters with specific expression patterns associated with certain phenotypic presentations, including late onset, autonomic neurological involvement, and gastrointestinal symptoms. This study provides novel data regarding the role of non-coding variation and the gene expression profiles in patients affected by TTR amyloidosis, also putting forth an approach that could be used to investigate the mechanisms at the basis of the genotype-phenotype correlation of the disease.
Two-dimensional in vitro cultures have represented a milestone in biomedical and pharmacological research. However, they cannot replicate the architecture and interactions of in vivo tissues. ...Moreover, ethical issues regarding the use of animals have triggered strategies alternative to animal models. The development of three-dimensional (3D) models offers a relevant tool to investigate disease pathogenesis and treatment, modeling in vitro the in vivo environment. We aimed to develop a dynamic 3D in vitro model for culturing human endothelial cells (ECs) and skin fibroblasts, simulating the structure of the tissues mainly affected in systemic sclerosis (SSc), a prototypical autoimmune fibrotic vasculopathy. Dermal fibroblasts and umbilical vein ECs grown in scaffold or hydrogel, respectively, were housed in bioreactors under flow. Fibroblasts formed a tissue-like texture with the deposition of a new extracellular matrix (ECM) and ECs assembled tube-shaped structures with cell polarization. The fine-tuned dynamic modular system allowing 3D fibroblast/EC culture connection represents a valuable model of the in vivo interplay between the main players in fibrotic vasculopathy as SSc. This model can lead to a more accurate study of the disease's pathogenesis, avoiding the use of animals, and to the development of novel therapies, possibly resulting in improved patient management.
Hereditary transthyretin amyloidosis (hATTR), alias ATTR variant (ATTRv) is a severe and disabling disease causing sensory and motor neuropathy, autonomic dysfunction, and cardiomyopathy. The ...progressive decline of patient's functional autonomy negatively affects the patient's quality of life and requires increasing involvement of relatives in the patient's daily life. Family caregiving may become particularly demanding when the patient is no longer able to move independently. This study is focused on the psychosocial aspects of ATTRv from the patient and relative perspectives. In particular, it explored: the practical and psychological burdens experienced by symptomatic patients with ATTRv and their key relatives and the professional and social network support they may rely on; whether burden varied in relation to patients' and relatives' socio-demographic variables, patients' clinical variables, and perceived professional and social network support; and, any difference in burden and support between patients and their matched relatives.
The study was carried out on symptomatic patients included in the ATTRv Italian national registry and living with at least one adult relative not suffering from severe illness and being free from ATTRv symptoms. Patients and relatives' assessments were performed using validated self-reported tools.
Overall, 141 patients and 69 relatives were evaluated. Constraints of leisure activities, feelings of loss and worries for the future were the consequences of ATTRv most frequently reported by patients and relatives. Both in patients and their relatives, the burden increased with the duration of symptoms and the level of help in daily activities needed by the patient. In the 69 matched patient-relative pairs, the practical burden was significantly higher among the patients than among their relatives, while the psychological burden was similar in the two groups. Moreover, compared to their relatives, patients with ATTRv reported higher levels of professional and social network support.
These results show that ATTRv is a disease affecting quality of life of both patients and their families. Supporting interventions should be guaranteed to patients, to facilitate their adaptation to the disease, and to their families, to cope as best as possible with the difficulties that this pathology may involve.
Somatic dysfunction (SD) is an altered body function involving the musculoskeletal system. However, its clinical signs-tissue texture abnormalities, positional asymmetry, restricted range of motion, ...and tissue tenderness-did not achieve satisfactory results for reliability. A recent theoretical model proposed a revision assessing the movement variability around the joint rest position. The asymmetry and restriction of motion may characterize functional assessment in osteopathic clinical practice, demonstrating the reliability required. Hence, this study investigated the reliability of the new variability model (VM) with gait analysis (GA). Three blind examiners tested 27 young healthy subjects for asymmetry of motion around rest position and the SD grade on six body regions. The results were compared to the VICON procedure for 3D-GA. The inter-rater agreement for the detection of reduced movement variability ranged from 0.78 to 0.54, whereas for SD, grade ranged from 0.64 to 0.47. VM had a sensitivity and specificity of 0.62 and 0.53, respectively, in SD detection compared to step length normality. Global severity grade of SD demonstrated moderate to good correlation with spatial-temporal parameters. The VM showed palpatory reliability and validity with spatial-temporal parameters in GA. Those findings contribute to the innovation for SD examination with implications for the clinical practice.
Key Clinical Message
Despite transient global amnesia is considered unusual in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and causal relation ...is still unclear, this report suggests to consider CADASIL in those patients with recurrent transient global amnesia, especially when MRI shows multifocal hyperintensities affecting the cerebral white matter or when it is followed by cognitive decline.
Despite transient global amnesia is considered unusual in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and causal relation is still unclear, this report suggests to consider CADASIL in those patients with recurrent transient global amnesia, especially when MRI shows multifocal hyperintensities affecting the cerebral white matter or when it is followed by cognitive decline.
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