Psychosocial predictors of upper extremity transplantation outcomes: A review of the international registry 1998–2016

Background: Upper extremity transplantation (UET) is becoming increasingly common. This article attempts to collate data from cases contributing to the International Registry on Hand and Composite Tissue Transplantation (IRHCTT), define psychosocial themes perceived as predictors of success using statistical methods, and provide an objective measure for optimization and selection of candidates. Methods: The IRHCTT provided anonymous data on UET recipients. A supple- mentary psychosocial survey was developed focusing on themes of depression, posttraumatic stress disorder (PTSD), anxiety, interpersonal functioning and dependence, compliance, chronic pain, social support, quality of life, and patient expectations. We determined the risk of transplant loss and psychological factors associated with higher risk of transplant loss. Results: Sixty-two UET recipients reported to the IRHCTT. Forty-three psychoso- cial surveys (68%) were received, with 38 (88%) having intact transplants and 5 (12%) being amputated. Among recipients with a diagnosis of anxiety (N = 29, 67%), 5 (17%) reported transplant loss (P = 0.03). Among those with depression (N = 14, 33%), 2 recipients (14%) has transplant loss (P = 0.17); while 4 recipients (22%) with PTSD (N = 18, 42%) had transplant loss (P = 0.01). Of participants active in occupational therapy (N = 28, 65%), 2 (7%) reported transplant loss (P = 0.09). Of recipients with realistic functional expectations (N = 34, 79%), 2 (6%) had transplant loss versus 3 (34%) who were felt to not have realistic expec- tations (N = 9, 21%, P = 0.05). Recipients with strong family support (N = 33, 77%) had a lower risk of transplant loss compared with poor or fair family support (N = 10, 23%), but did not reach statistical significance (6% versus 30%, P = 0.14). Conclusion: Anxiety, depression, PTSD, participation in occupational therapy, expectations for posttransplant function, and family support are associated with postsurgical transplant status

Comparison of Ferments in the Process of Functional Beverage Making

The aim of this study was to compare the main ferments selected to be used in the process of mead making: Saccharomyces cerevisiae yeast and pollen, the latter having been used in ancient times as ferment. It has only been recently that the market has exhibited significant interest in developing foods containing functional ingredients. Honey has been a corollary of hidden nutritional and medicinal value for centuries. Mead is the result of alcoholic fermentation, by mixing different proportions of honey with water and pollen, as a fermentation agent. The fermentation process was monitored by collecting samples periodically and analyzing the alcohol concentration, total extract, the level of fermentation, the pH, as well as the yeast number with the Thoma cell counting chamber. Additionally, physicochemical (acidity and vitamin C) and sensory parameters were determined for the final products. Results and discussion: Pollen-fermented beverages have a higher alcohol concentration than beverages fermented with Saccharomyces cerevisiae, which is explained by the additional intake of carbohydrates induced by the addition of pollen

Causal relevance of blood lipid fractions in the development of carotid atherosclerosis: Mendelian randomization analysis.

BACKGROUND: Carotid intima-media thickness (CIMT), a subclinical measure of atherosclerosis, is associated with risk of coronary heart disease events. Statins reduce progression of CIMT and coronary heart disease risk in proportion to the reduction in low-density lipoprotein cholesterol. However, interventions targeting triglycerides (TGs) or high-density lipoprotein cholesterol (HDL-C) have produced inconsistent effects on CIMT and coronary heart disease risk, making it uncertain whether such agents are ineffective for coronary heart disease prevention or whether CIMT is an inadequate marker of HDL-C or TG-mediated effects. We aimed to determine the causal association among the 3 major blood lipid fractions and common CIMT using mendelian randomization analysis. METHODS AND RESULTS: Genetic scores specific for low-density lipoprotein cholesterol, HDL-C, and TGs were derived based on single nucleotide polymorphisms from a gene-centric array in ≈5000 individuals (Cardiochip scores) and from a genome-wide association meta-analysis in >100 000 individuals (Global Lipids Genetic Consortium scores). These were used as instruments in a mendelian randomization analysis in 2 prospective cohort studies. A genetically predicted 1 mmol/L higher low-density lipoprotein cholesterol concentration was associated with a higher common CIMT by 0.03 mm (95% confidence interval, 0.01-0.04) and 0.04 mm (95% confidence interval, 0.02-0.06) based on the Cardiochip and Global Lipids Genetic Consortium scores, respectively. HDL-C and TGs were not causally associated with CIMT. CONCLUSIONS: Our findings confirm a causal relationship between low-density lipoprotein cholesterol and CIMT but not with HDL-C and TGs. At present, the suitability of CIMT as a surrogate marker in trials of cardiovascular therapies targeting HDL-C and TGs is questionable and requires further study

Optogenetic Peripheral Nerve Immunogenicity

Optogenetic technologies have been the subject of great excitement within the scientific community for their ability to demystify complex neurophysiological pathways in the central (CNS) and peripheral nervous systems (PNS). The excitement surrounding optogenetics has also extended to the clinic with a trial for ChR2 in the treatment of retinitis pigmentosa currently underway and additional trials anticipated for the near future. In this work, we identify the cause of loss-of-expression in response to transdermal illumination of an optogenetically active peroneal nerve following an anterior compartment (AC) injection of AAV6-hSyn-ChR2(H134R) with and without a fluorescent reporter. Using Sprague Dawley Rag2−/− rats and appropriate controls, we discover optogenetic loss-of-expression is chiefly elicited by ChR2-mediated immunogenicity in the spinal cord, resulting in both CNS motor neuron death and ipsilateral muscle atrophy in both low and high Adeno-Associated Virus (AAV) dosages. We further employ pharmacological immunosuppression using a slow-release tacrolimus pellet to demonstrate sustained transdermal optogenetic expression up to 12 weeks. These results suggest that all dosages of AAV-mediated optogenetic expression within the PNS may be unsafe. Clinical optogenetics for both PNS and CNS applications should take extreme caution when employing opsins to treat disease and may require concurrent immunosuppression. Future work in optogenetics should focus on designing opsins with lesser immunogenicity.MIT Media Lab Consortiu

Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients

Phenylketonuria (PKU, OMIM 261600) is predominantly caused by mutations in the PAH gene. One hundred and three Argentine PKU patients were studied by Sanger sequencing; 101 were completely characterized (90.3% were compound heterozygotes). Fifty-four different pathogenic variants were identified. Mutations were distributed all along the PAH gene but concentrated in exon 7 (26%), 12 (12%), 11 (10%), and 6 (10%). 77% were missense, and 77% affected the enzyme catalytic domain, nine mutations accounted for 57% of 179 studied alleles: p.Arg261Gln (Allele frequency(AF):10.6%), c.1066-11G>A (AF:9,5%), p.Arg408Trp (AF:8,3%), p.Tyr414Cys (AF:5,5%), p.Ala403Val, p.Val388Met, and p.Arg158Gln (AF: 5% each), p.Leu48Ser, and p.Ile65Thr (AF:4% each). The predicted phenotype was assigned by Guldberg´s arbitrary value (AV) and compared with the clinical phenotype based in tolerance to Phe intake. 29.1% (n:30) were hyperphenylalaninemias, 18.5% (n:19) mild-PKU, 27.2% (n:28) moderate-PKU and 25.2 % (n:26) classical-PKU. Genotype/phenotype correlation was statistically significant (p<0.001) Overall concordance was 62,5%: 93.3% in hyperphenylalaninemia, 64.7% in mild-PKU and 65.4% in classical patients. The moderate-PKU showed a weak concordance (17%) with milder AV prediction than clinical assessment. 74% of discordant moderate patients harbored p.Arg261Gln, and p.Val388Met. Our cohort is highly heterogeneous, with predominant Mediterranean influence (mainly Spanish), but with differences with other Latin-American countries.Fil: Enacán, Rosa E.. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Miñana, Mariana Nuñez. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Fernandez, Luis. Universidad Autónoma de Madrid; EspañaFil: Valle, María Gabriela. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Salerno, Mercedes. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Fraga, Claudia I.. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Santos Simarro, Fernando. Universidad Autónoma de Madrid; EspañaFil: Prieto, Laura. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Lapunzina, Pablo. Universidad Autónoma de Madrid; EspañaFil: Specola, Norma. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Fundacion de Endocrinologia Infantil.; Argentin

Interannual fuctuations in connectivity among crab populations (Liocarcinus depurator) along theAtlantic‑Mediterranean transition

An interesting evolutionary question that still remains open is the connectivity between marine populations. Marine currents can favour the dispersal of larvae or adults, but they can also produce eddies and gyres generating oceanographic fronts, thus limiting gene flow. To address this subject, we selected the Atlantic-Mediterranean transition, where several fronts are located: Gibraltar Strait (GS), Almeria-Oran Front (AOF) and Ibiza Channel (IC). Seven populations of the marine crab Liocarcinus depurator (Cadiz, West and East Alboran, Alacant, Valencia, Ebro Delta and North Catalonia) located along this transition were analysed in six consecutive years (2014–2019) using a fragment of the COI (Cytochrome Oxidase subunit I) gene. All sequences (966) belonged to two well defined haplogroups: ATL (most abundant in Atlantic waters) and MED (predominant in Mediterranean waters). Following a geographic variation, the frequency of ATL decreased significantly from Cadiz to North Catalonia. However, this variation presented steps due to the effect of oceanographic restrictions/fronts. Significant effects were recorded for GS (2015, 2017, 2018 and 2019), AOF (all years except 2018) and IC (2016). The intensity and precise location of these fronts changed over time. Multivariate analyses distinguished three main population groups: Cadiz, Alboran Sea and the remaining Mediterranean populations. These findings could be relevant to properly define Marine Protected Areas and for conservation and fisheries policies

Hard-core/zeolitized-shell beads obtained by surface zeolitization of activated clay particles

This work presents a novel and cost-effective procedure that improves the reactivity of kaolinitic clay particles toward the generation of millimetric hard-core/zeolitized-shell units. The obtained particulate material is ready to use as ion exchanger beads in a fixed adsorption bed. Starting from properly activated, millimeter-sized clay units, the transition of their external surface towards a new crystalline ordering could be induced. The Na₂CO₃ alkaline activation treatment applied to previously calcined clay particles allowed obtaining different levels of NaAlSiO₄ polymorphs on the external surface of the particles, which are easily transformed to zeolitic products. By varying the synthesis conditions, FAU and LTA zeolite structures were successfully obtained on the surface of hardened particles, reaching conversions close to 90%. The starting clay, pretreated clays, and products obtained after hydrothermal synthesis were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray microanalysis (EDX). The versatility of the method is exemplified in obtaining adsorbents specifically designed for the retention of Cd²⁺ and Ni²⁺ contaminating ions. A total removal of Cd²⁺ and Ni²⁺ was achieved at 150 min from initial 40 ppm solutions, being 98% and 94% from initial 120 ppm solutions for cadmium and nickel, respectively.Centro de Investigación y Desarrollo en Ciencias AplicadasCentro de Tecnología de Recursos Minerales y Cerámic

2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography Deauville scale and core-needle biopsy to determine successful management after six doxorubicin, bleomycin, vinblastine and dacarbazine cycles in advanced-stage Hodgkin lymphoma.

Abstract Background The clinical impact of the positivity of the Deauville scale (DS) of positron emission tomography (PET) performed at the end of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) in patients with advanced Hodgkin lymphoma (HL), in terms of providing rationale to shift poor responders onto a more intensive regimen, remain to be validated by histopathology. Patients and methods This prospective trial involved patients with stage IIB/IV HL who after six ABVD cycles underwent PET (PET6) and core-needle cutting biopsy (CNCB) of 2-deoxy-2[F-18] fluoro- d -glucose (FDG)-avid lymph nodes. Patients received high-dose chemotherapy/autologous haematopoietic stem cell rescue (HDCT/AHSCR) if CNCB was positive for HL, alternatively, if CNCB or PET was negative, received observation or consolidation radiotherapy (cRT) on residual nodal masses, as initially planned. The end-point was 5-year progression-free survival (PFS). Results In all, 43 of the 169 (25%) evaluable patients were PET6 positive (DS 4, 32; DS 5, 11). Among them, histology showed malignancy (HL) in 100% of DS 5 scores and in 12.5% of DS 4 scores. Fifteen patients with positive biopsy received HDCT/AHSCR, whereas 28 patients with negative biopsy, as well as 126 patients with negative PET6, continued the original plan (cRT, 78 patients; observation, 76 patients). The 5-year PFS in the negative PET6 group, negative biopsy group and positive biopsy group was 95.4%, 100% and 52.5%, respectively. Conclusion DS positivity of end-of-ABVD PET in advanced HL carried a certain number of CNCB-proven non-malignant FDG-uptakes. The DS 4 scores which were found to have negative histology appeared to benefit from continuing the original non-intensive therapeutic plane as indicated by the successful outcome in more than 95% of them by obtaining similar 5-year PFS to the PET6-negative group. By contrast, the DS 5 score had consistently positive histology and was associated with unsuccessful conventional therapy, promptly requiring treatment intensification or innovative therapeutic approaches

Multi-compartment analysis of the complex gradient-echo signal quantifies myelin breakdown in premanifest Huntington's disease

White matter (WM) alterations have been identified as a relevant pathological feature of Huntington’s disease (HD). Increasing evidence suggests that WM changes in this disorder are due to alterations in myelin‐associated biological processes. Multi-compartmental analysis of the complex gradient-echo MRI signal evolution in WM has been shown to quantify myelin in vivo, therefore pointing to the potential of this technique for the study of WM myelin changes in health and disease. This study first characterized the reproducibility of metrics derived from the complex multi-echo gradient-recalled echo (mGRE) signal across the corpus callosum in healthy participants, finding highest reproducibility in the posterior callosal segment. Subsequently, the same analysis pipeline was applied in this callosal region in a sample of premanifest HD patients (n = 19) and age, sex and education matched healthy controls (n = 21). In particular, we focused on two myelin-associated derivatives: i. the myelin water signal fraction (fm), a parameter dependent on myelin content; and ii. the difference in frequency between myelin and intra-axonal water pools (Δω), a parameter dependent on the ratio between the inner and the outer axonal radii. fm was found to be lower in HD patients (β = -0.13, p = 0.03), while Δω did not show a group effect. Performance in tests of working memory, executive function, social cognition and movement was also assessed, and a greater age-related decline in executive function was detected in HD patients (β = -0.06, p = 0.006), replicating previous evidence of executive dysfunction in HD. Finally, the correlation between fm, executive function, and proximity to disease onset was explored in patients, and a positive correlation between executive function and fm was detected (r = 0.542; p = 0.02). This study emphasises the potential of complex mGRE signal analysis for aiding understanding of HD pathogenesis and progression. Moreover, expanding on evidence from pathology and animal studies, it provides novel in vivo evidence supporting myelin breakdown as an early feature of HD