Fibroblasts and Endothelial Cells in Three-Dimensional Models: A New Tool for Addressing the Pathogenesis of Systemic Sclerosis as a Prototype of Fibrotic Vasculopathies.

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.

Reliability and Validity of the Variability Model Testing Procedure for Somatic Dysfunction Assessment: A Comparison with Gait Analysis Parameters in Healthy Subjects.

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.

Psychosocial burden and professional and social support in patients with hereditary transthyretin amyloidosis (ATTRv) and their relatives in Italy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

ATTRv amyloidosis Italian Registry: clinical and epidemiological data.

INTRODUCTION: ATTRv amyloidosis is worldwide spread with endemic foci in Portugal and Sweden, Japan, Brazil, Maiorca, and Cyprus. A national Registry was developed to characterise the epidemiology and genotype-phenotype correlation of ATTRv amyloidosis in Italy and to allow a better planning of diagnostic and therapeutic services. METHODS: Fifteen Italian referral centres for amyloidosis spread all over the country have contributed to the Registry. RESULTS: Four-hundred-forty-seven subjects were enrolled, 187 asymptomatic carriers and 260 affected patients. Thirty-one different mutations were recorded. The seven most represented genetic variants were significantly different in terms of age at onset, clinical features and geographical distribution. National prevalence is 4.33/million with higher values in Southern Italy. Overall symptoms of polyneuropathy were present at disease onset in about half of the patients, symptoms of cardiomyopathy in a quarter of patients, the rest referring carpal tunnel syndrome, dysautonomia or lumbar spinal stenosis. 52.6% of patients were in FAP stage 1, 20.4% in stage 2 and 13.5% in stage 3, while 13.5% patients had no neuropathy, presenting only cardiological symptoms. CONCLUSIONS: We presented an epidemiological study based on collaboration among referral centres for ATTRv amyloidosis spread in all the Italian territory, using web-based Registry. It provided a detailed map of the regional distribution of the disease. The increased awareness of the disease among general practitioners and medical specialists has contributed to reduce the diagnostic delay and the rate of misdiagnosis. The Registry will allow to collect also future information about clinical and instrumental follow-up.

Severe Postoperative Chronic Constipation Related to Anorectal Malformation Managed with Osteopathic Manipulative Treatment.

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.

Utility of Boston Qualitative Scoring System for Rey-Osterrieth Complex Figure: evidence from a Parkinson's Diseases sample.

This study examined the ability of the Boston Qualitative Scoring System (BQSS) in comparison to the Osterrieth scoring method to separate Parkinson's Disease patients without dementia from healthy controls at the Rey-Osterrieth Complex Figure (ROCF) copy. 30 PD participants and 30 healthy participants completed ROCF copy. The performance was scored according to both methods. The results indicated that PD patients performed significantly worse on ROCF. According to ROC analyses, BQSS Copy Total score represented the most suitable index to distinguish between the two groups: a score below or equal to 16 indicates an impaired performance. Moreover, PD participants reported lower performance in the BQSS scores of Planning and Neatness. PD patients' poor performance in ROCF copy was related to executive difficulties, specifically in terms of planning and impulsivity, instead of global visuo-constructional impairments. An extensive evaluation of copy drawings allowing to disentangle between different involved cognitive domains would be suitable, specifically in those clinical conditions like PD, in which motor impairments affect drawing performance.