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Data on residual clinical damage after Coronavirus disease-2019 (COVID-19) are lacking. The aims of this study were to investigate whether COVID-19 leaves behind residual dysfunction, and identify patients who might benefit from post-discharge monitoring. All patients aged ≥18 years admitted to the Emergency Department (ED) for COVID-19, and evaluated at post-discharge follow-up between 7 April and 7 May, 2020, were enrolled. Primary outcome was need of follow-up, defined as the presence at follow-up of at least one among: respiratory rate (RR) >20 breaths/min, uncontrolled blood pressure (BP) requiring therapeutic change, moderate to very severe dyspnoea, malnutrition, or new-onset cognitive impairment, according to validated scores. Post-traumatic stress disorder (PTSD) served as secondary outcome. 185 patients were included. Median [interquartile range] time from hospital discharge to follow-up was 23 [20-29] days. 109 (58.9%) patients needed follow-up. At follow-up evaluation, 58 (31.3%) patients were dyspnoeic, 41 (22.2%) tachypnoeic, 10 (5.4%) malnourished, 106 (57.3%) at risk for malnutrition. Forty (21.6%) patients had uncontrolled BP requiring therapeutic change, and 47 (25.4%) new-onset cognitive impairment. PTSD was observed in 41 (22.2%) patients. At regression tree analysis, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) and body mass index (BMI) at ED presentation, and age emerged as independent predictors of the need of follow-up. Patients with PaO2/FiO2 <324 and BMI ≥33 Kg/m2 had the highest odds to require follow-up. Among hospitalised patients, age ≥63 years, or age <63 plus non-invasive ventilation or diabetes identified those with the highest probability to need follow-up. PTSD was independently predicted by female gender and hospitalisation, the latter being protective (odds ratio, OR, 4.03, 95% confidence interval, CI, 1.76 to 9.47, p 0.0011; OR 0.37, 95% CI 0.14 to 0.92, p 0.033, respectively). COVID-19 leaves behind physical and psychological dysfunctions. Follow-up programmes should be implemented for selected patients.

ABSTRACT : The introduction of modular design in total hip arthroplasty has enabled the use of different materials in one single configuration and the adjustment of the prosthesis to the patient’s body, and facilitated medical revisions. However, modularity leads to the presence of new interfaces created between pieces in contact, raising the issue of degradation. Tribocorrosion phenomena have been identified as the main degradation mechanism due to the mechanical, chemical, and electrochemical conditions acting on the materials. In addition, conditions inside the human body are unclear, regarding electrochemical settings and the interaction between the electrochemical and mechanical action. This work is focused on the degradation of monopolar hip joint implants made from biomedical alloys such as stainless steel, Ti, and CoCr alloys. Three cases are presented and analyzed in terms of the degradation level along the trunnion length. Surface analysis done on a titanium trunnion showed a significant ploughing on the distal part, compared to what was found for stainless steel and cobalt-chromium alloys, which can produce a stuck in this area. Meanwhile, in the proximal part, wear debris is found, which suggests more movement in the internal part. Although few debris particles were identified in CoCr trunnion, a large amount of material inside the contact was observed. This could be related to the ploughing generated in the distal thread pattern, which allowed the material to come inside and outside the contact.

ObjectivesPathogenic variants in AIFM1 have been associated with a wide spectrum of disorders, spanning from CMT4X to mitochondrial encephalopathy. Here we present a novel phenotype and review the existing literature on AIFM1-related disorders.MethodsWe performed EEG recordings, brain MRI and MR Spectroscopy, metabolic screening, echocardiogram, clinical exome sequencing (CES) and family study. Effects of the variant were established on cultured fibroblasts from skin punch biopsy.ResultsThe patient presented with drug-resistant, electro-clinical, multifocal seizures 6 h after birth. Brain MRI revealed prominent brain swelling of both hemispheres and widespread signal alteration in large part of the cortex and of the thalami, with sparing of the basal nuclei. CES analysis revealed the likely pathogenic variant c.5T>C; p.(Phe2Ser) in the AIFM1 gene. The affected amino acid residue is located in the mitochondrial targeting sequence. Functional studies on cultured fibroblast showed a clear reduction in AIFM1 protein amount and defective activities of respiratory chain complexes I, III and IV. No evidence of protein mislocalization or accumulation of precursor protein was observed. Riboflavin, Coenzyme Q10 and thiamine supplementation was therefore given. At 6 months of age, the patient exhibited microcephaly but did not experience any further deterioration. He is still fed orally and there is no evidence of muscle weakness or atrophy.InterpretationThis is the first AIFM1 case associated with neonatal seizures and diffuse white matter involvement with relative sparing of basal ganglia, in the absence of clinical signs suggestive of myopathy or motor neuron disease.

Background Recurrent (RP) and chronic pancreatitis (CP) may complicate Cystic Fibrosis (CF). It is still unknown if mutations in genes involved in the intrapancreatic activation of trypsin (IPAT) or in the pancreatic secretion pathway (PSP) may enhance the risk for RP/CP in patients with CF. Methods We enrolled: 48 patients affected by CF complicated by RP/CP and, as controls 35 patients with CF without pancreatitis and 80 unrelated healthy subjects. We tested a panel of 8 genes involved in the IPAT, i.e. PRSS1, PRSS2, SPINK1, CTRC, CASR, CFTR, CTSB and KRT8 and 23 additional genes implicated in the PSP. Results We found 14/48 patients (29.2%) with mutations in genes involved in IPAT in the group of CF patients with RP/CP, while mutations in such genes were found in 2/35 (5.7%) patients with CF without pancreatitis and in 3/80 (3.8%) healthy subjects ( p  < 0.001). Thus, we found mutations in 12 genes of the PSP in 11/48 (22.9%) patients with CF and RP/CP. Overall, 19/48 (39.6%) patients with CF and RP/CP showed one or more mutations in the genes involved in the IPAT and in the PSP while such figure was 4/35 (11.4%) for patients with CF without pancreatitis and 11/80 (13.7%) for healthy controls ( p  < 0.001). Conclusions The trans-heterozygous association between CFTR mutations in genes involved in the pathways of pancreatic enzyme activation and the pancreatic secretion may be risk factors for the development of recurrent or chronic pancreatitis in patients with CF.

Genetic features of chronic pancreatitis (CP) have been investigated extensively, mainly by testing genes associated to the trypsinogen activation pathway. However, different molecular pathways involving other genes may be implicated in CP pathogenesis. A total of 80 patients with idiopathic chronic pancreatitis (ICP) were investigated using a Next-Generation Sequencing (NGS) approach with a panel of 70 genes related to six different pancreatic pathways: premature activation of trypsinogen, modifier genes of cystic fibrosis phenotype, pancreatic secretion and ion homeostasis, calcium signaling and zymogen granules (ZG) exocytosis, autophagy and autoimmune pancreatitis-related genes. We detected mutations in 34 out of 70 genes examined; of the 80 patients, 64 (80.0%) were positive for mutations in one or more genes and 16 (20.0%) had no mutations. Mutations in CFTR were detected in 32 of the 80 patients (40.0%) and 22 of them exhibited at least one mutation in genes of other pancreatic pathways. Of the remaining 48 patients, 13/80 (16.3%) had mutations in genes involved in premature activation of trypsinogen and 19/80 (23.8%) had mutations only in genes of the other pathways: 38 (59.3%) of the 64 patients positive for mutations showed variants in two or more genes. Our data, although to be extended with functional analysis of novel mutations, suggest a high rate of genetic heterogeneity in CP and that trans-heterozygosity may predispose to the ICP phenotype.

El uso de implantes modulares de cadera ha permitido el uso de diferentes materiales en un solo dispositivo, un mejor ajuste a la anatomía del paciente y, ha facilitado los procedimientos de revisión. Sin embargo, dicha modularidad crea nuevas interfaces que pueden sufrir degradación por mecanismos triboquímicos como fretting - corrosión, por las condiciones mecánicas, químicas y electroquímicas propias del cuerpo. Actualmente, dichas condiciones no son completamente claras, ni la interacción ellas. Este trabajo se centra en el análisis de la degradación de implantes mono-polares de cadera elaborados en aleaciones biomédicas: acero inoxidable (SS), aleaciones de Ti y C°Cr, en los que se analiza el nivel de degradación a lo largo de la longitud del cono femoral. El cono femoral de titanio mostró una deformación más significativa de la zona distal que causa un bloqueo entre las partes modulares, comparado con la misma zona de partes fabricadas en SS y aleaciones cobalto-cromo. Por otra parte, partículas de desgaste fueron encontradas en la parte proximal, lo que sugiere que esta es una zona bajo mayor movimiento. En el cono femoral de C°Cr pudo observarse una gran cantidad de material orgánico dentro del contacto. Lo anterior pudo ser causado por un ajuste deficiente inferido por la baja deformación en los filetes de la zona distal, lo que probablemente promovió que más material entrara y saliera del contacto.

BackgroundThe effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies.ObjectivesTo describe the genotype–phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator (CFTR) complex alleles.MethodsWe studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele.ResultsThe p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I–II mutation. Their CFTR activity on NEC was comparable with patients with two class I–II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I–II mutation in trans, or CFTR-related disorders (CFTR-RD) in three having in trans a class IV–V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (p<0.001) higher CFTR activity compared with compound heterozygous for class I–II mutations. Furthermore, five of six compounds heterozygous with the p.[Arg117Leu;Leu997Phe] had mild CF, whereas the p.Leu997Phe, in trans with a class I–II CFTR mutation, caused CFTR-RD or a healthy status (CFTR activity: 21.3–36.9%). Finally, compounds heterozygous for the c.[1210-34TG[12];1210-12T[5];2930C>T] and a class I–II mutation had mild CF or CFTR-RD (gating activity: 18.5–19.0%).ConclusionsThe effect of complex alleles partially depends on the mutation in trans. Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction.

TNXB-related classical-like Ehlers-Danlos syndrome (TNXB-clEDS) is an ultrarare type of Ehlers-Danlos syndrome due to biallelic null variants in TNXB, encoding tenascin-X. Less than 30 individuals have been reported to date, mostly of Dutch origin and showing a phenotype resembling classical Ehlers-Danlos syndrome without atrophic scarring. TNXB-clEDS is likely underdiagnosed due to the complex structure of the TNXB locus, a fact that complicates diagnostic molecular testing. Here, we report two unrelated Italian women with TNXB-clEDS due to compound heterozygosity for null alleles in TNXB. Both presented soft and hyperextensible skin, generalized joint hypermobility and related musculoskeletal complications, and chronic constipation. In addition, individual 1 showed progressive finger contractures and shortened metatarsals, while individual 2 manifested recurrent subconjunctival hemorrhages and an event of spontaneous rupture of the brachial vein. Molecular testing found the two previously unreported c.8278C > T p.(Gln2760*) and the c.(2358 + 1_2359 − 1)_(2779 + 1_2780 − 1)del variants in Individual 1, and the novel c.1150dupG p.(Glu384Glyfs*57) and the recurrent c.11435_11524+30del variants in Individual 2. mRNA analysis confirmed that the c.(2358 + 1_2359 − 1)_(2779 + 1_2780 − 1)del variant causes a frameshift leading to a predicted truncated protein [p.(Thr787Glyfs*40)]. This study refines the phenotype recently delineated in association with biallelic null alleles in TNXB, and adds three novel variants to its mutational repertoire. Unusual digital anomalies seem confirmed as possibly peculiar of TNXB-clEDS, while vascular fragility could be more than a chance association also in this Ehlers-Danlos syndrome type.

El uso incidental y no autorizado de obras protegidas y marcas registradas en producciones audiovisuales es una práctica que no está resuelta legalmente. Este artículo analizará la viabilidad legal de esta práctica, abordando tensiones relacionadas con los riesgos del uso incidental de obras protegidas y marcas bajo las normas de la Comunidad Andina y experiencias internacionales. Se analizarán las bases interpretativas dispuestas por el Tribunal de Justicia de la Comunidad Andina sobre el uso incidental de obras pictóricas en obras audiovisuales, para analizar su aplicabilidad a todo tipo de imágenes visuales y a marcas en obras audiovisuales. Este estudio busca analizar el criterio incidental en obras audiovisuales para ofrecer un marco teórico aplicable a la industria audiovisual y dirigido a cineastas, productores audiovisuales, y abogados en derecho del entretenimiento.

With the growth of the luxury industry in recent years, especially the personal goods segment, and with environmental concerns and sustainability increasingly influencing consumers, it is crucial to understand the role of this industry in the spotlight of sustainability.For this reason, this investigation aims to understand what perceptions, feelings, and purchase intentions current and potential consumers will have about these sustainable luxury products. To do this, based on the literature, information was gathered from individuals by (1) developing a questionnaire to assess consumers’ perceptions and attitudes towards different sustainable strategies, and (2) conduction interviews to deepen the knowledge regarding consumer’s emotions regarding sustainable luxury products. This way, it was possible to assess people's perspectives and understanding of the new sustainable production methods that have been implemented. The results of this investigation reveal that, in general, individuals are considerably concerned about the current state of the environment and that despite their positive purchase intentions for this type of sustainable goods, perceptions about them are not unanimous and deserve further look.Thus, this study provides relevant academic and managerial contributions, as it indicates which sustainable strategies are most familiar to individuals, how they judge and evaluate them, and which of them generates higher purchase intentions, granting a deeper knowledge about the potential consumers in this market segment.