Current Technologies and Practices to Assess External Training Load in Paralympic Sport: A Systematic Review.

CONTEXT: Knowing the methods to assess the external load in Paralympic sports can help multidisciplinary teams rely on scientific evidence to better prescribe and monitor the athlete's development, improving sports performance and reducing the risk of injury/illness of Paralympic athletes. OBJECTIVES: This review aimed to systematically explore the current practices of quantifying the external load in Paralympic sports and provide an overview of the methods and techniques used. EVIDENCE ACQUISITION: A search in PubMed, Web of Science, Scopus, and EBSCO was carried out until November 2022. The measures of interest were objective methods for quantifying the external load of training or competition. The inclusion criteria for the studies were as follows: (1) peer-reviewed article; (2) the population were Paralympic athletes; (3) evaluated during training or competition; (4) reported at least one external load measure; and (5) published in English, Portuguese, or Spanish. EVIDENCE SYNTHESIS: Of the 1961 articles found, 22 were included because they met the criteria, and 8 methods were identified to quantify the external load in training or competition in 8 Paralympic sports. The methods varied according to the characteristics of the Paralympic sports. To date, the devices used included an internal radiofrequency-based tracking system (wheelchair rugby) a miniaturized data logger (wheelchair tennis, basketball, and rugby); a linear position transducer (powerlifting and wheelchair basketball); a camera (swimming, goalball, and wheelchair rugby); a global positioning system (wheelchair tennis); heart rate monitors that assess external load variables in set (paracycling and swimming) and an electronic timer (swimming). CONCLUSIONS: Different objective methods were identified to assess the external load in Paralympic sports. However, few studies showed the validity and reliability of these methods. Further studies are needed to compare different methods of external load quantification in other Paralympic sports.

Impact of exercise intervention-based changes on physical function biomarkers in older adults after hospital discharge: A systematic review with meta-analysis of randomized clinical trials.

BACKGROUND: This systematic review with meta-analysis aimed to compare the changes caused by exercise intervention with those provoked by usual care on physical function biomarkers in older adults immediately after hospital discharge. METHODS: Two independent authors performed a systematic search (PubMed, Scopus, Web of Science, and SciELO) of studies published from database inception until August 2021. Randomized clinical trials investigating the effects of an exercise intervention compared to usual care were included. The Cochrane Collaboration assessment tool was used to analyze the risk of bias. The comparisons included handgrip strength, the short physical performance battery scale, six-minute walking test, and 10-m gait speed. RESULTS: Overall, the exercise intervention led to significantly greater changes compared to usual care in physical function biomarkers [standard mean difference = 0.89, 95% CI = 0.39, 1.42; P = 0.001]. However, considering the very few studies investigating each variable separately, our sub-analysis did not reveal a significant effect of the exercise intervention on handgrip strength, the short physical performance battery, six minutes walking test, and 10-m gait speed. CONCLUSIONS: This systematic review with meta-analysis of randomized clinical trials suggests that exercise intervention induce greater physical function biomarker alterations in older adults after hospitalization than usual care including physical activity guidance. Future trials comparing the effects of these intervention groups on physical function biomarkers in this population are needed to confirm our results.

Blocking EGFR with nimotuzumab: a novel strategy for COVID-19 treatment.

Background: Lung injury and STAT1 deficit induce EGFR overexpression in SARS-CoV-2 infection. Patients & methods: A phase I/II trial was done to evaluate the safety and preliminary effect of nimotuzumab, an anti-EGFR antibody, in COVID-19 patients. Patients received from one to three infusions together with other drugs included in the national guideline. Results: 41 patients (31 severe and 10 moderate) received nimotuzumab. The median age was 62 years and the main comorbidities were hypertension, diabetes and cardiovascular disease. The antibody was very safe and the 14-day recovery rate was 82.9%. Inflammatory markers decreased over time. Patients did not show signs of fibrosis. Conclusion: Nimotuzumab is a safe antibody that might reduce inflammation and prevent fibrosis in severe and moderate COVID-19 patients. Clinical Trial Registration: RPCEC00000369 (rpcec.sld.cu).

Background: After SARS-CoV-2 infection, many cells in the lung express a new receptor called EGFR. Overexpression of EGFR can worsen the pulmonary disease and provoke fibrosis. Patients & methods: The initial impact of using a drug that blocks EGFR, nimotuzumab, was evaluated in COVID-19 patients. Results: 41 patients received nimotuzumab by the intravenous route together with other medications. The median age was 62 years, and patients had many chronic conditions including hypertension, diabetes and cardiac problems. Treatment was well tolerated and 82.9% of the patients were discharged by day 14. Serial laboratory tests, x-rays and CT scan evaluations showed the improvement of the patients. Conclusion: Nimotuzumab is a safe drug that can be useful to treat COVID-19 patients.

Miopía en pacientes con retinopatía de la prematuridad / Myopia in patients with Retinopathy of Prematurity

Objetivos: describir el comportamiento del defecto miópico hasta el año de vida, en pacientes que desarrollaron retinopatía de la prematuridad, y determinar los principales factores de riesgo del mismo. Método: se realizó un estudio descriptivo, longitudinal, prospectivo en 37 pacientes que, habiendo sido tratados o no por retinopatía de la prematuridad, mantuvieron un seguimiento estable en consulta posterior a la fase aguda de la enfermedad. Fueron evaluadas a los seis y 12 meses de vida teniendo en cuenta las variables edad gestacional al nacer, peso al nacer, tipo de retinopatía de la prematuridad, presencia de miopía. Resultados: la mediana de edad gestacional y peso al nacer fueron 30,2 semanas y 1 287 g. A los seis meses cinco ojos de 27 pacientes (considerando solo los ojos derechos) presentaron miopía, lo cual representa el 18,5 por ciento. A los 12 meses este valor se incrementó a 44,4 por ciento. La edad gestacional y el peso al nacer no mostraron relación con el desarrollo de miopía (p = 0,072 y p = 0,397) a los 12 meses. En pacientes con retinopatía de la prematuridad grave el defecto miópico resultó más frecuente (p = 0,003). Conclusiones: la prematuridad y el peso al nacer no constituyeron variables que influyeran en la aparición de miopía. Por el contrario, la retinopatía de la prematuridad grave sí se asoció con una mayor miopía, sobre todo a los 12 meses(AU)

Objectives: to describe the behavior of the myopic defect up to one year of life, in patients who developed retinopathy of prematurity, and to determine the main risk factors for it. Method: a descriptive, longitudinal, prospective study was carried out in 37 patients who, having been treated for retinopathy of prematurity or not, maintained a stable follow-up in consultation after the acute phase of the disease. They were evaluated at 6 and 12 months of life taking into account the variables gestational age at birth, birth weight, type of retinopathy of prematurity, presence of myopia. Results: Median gestational age and birth weight were 30.2 weeks and 1287g. At 6 months, 5 eyes of 27 patients (considering only the right eyes) presented myopia, which represents 18.5 percent. At 12 months this value increased to 44.4 percent. Gestational age and birth weight were not related to the development of myopia (p = 0.072) and p = 0.397) at 12 months. In patients with severe retinopathy of prematurity, myopic defect was more frequent (p = 0.003). Conclusions: prematurity and birth weight were not variables that influenced the appearance of myopia. On the contrary, severe retinopathy of prematurity was associated with greater myopia, especially at 12 months(AU)

Diagnostic performance of LI-RADS in adult patients with rare hepatic tumors.

OBJECTIVE: The rare hepatic tumor can have a wide spectrum of radiologic features, representing a diagnostic challenge. Our purpose is to report the experience of a National Cancer Center, emphasizing the radiological features encountered and assessing the LR-M categories in the diagnostic performances for these lesions. PATIENTS AND METHODS: We assessed 113 patients who underwent surgical resection or biopsy for rare liver lesions from May 2010 to December 2020. For these patients a computerized search of radiological records was performed to identify which had been studied with MRI and CT. For each lesion, the radiologists recorded the attenuation on CT studies and signal intensity (SI) in T1 weighted (W), in T2-W, DWI and in the related map of the apparent diffusion coefficient (ADC). We assessed the presence and the type of contrast enhancement (CE) during contrast study on CT and MRI and the enhancement was categorized according to LI-RADS 2018. We also assessed the presence of other features in LR-M categories (ancillary LR-M features) in order to classify different subgroups. The lesions were classified according to LR categories, and the gold standard was histological analysis. RESULTS: The final study population included 95 patients (46 females and 49 males), with a mean age of 51 years (range 38-83 years). 83 patients had solid lesions, 12 patients had cystic lesions (simple or complex). According to histological analysis, we categorized 79 patients with malignant lesions and 16 patients with benign lesions. According to radiological features we assessed as malignant 82 patients (79 true malignant and 3 false malignant), as benign 13 patients (all true benign). Therefore, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of radiological features to identify benign and malignant lesions were 100.0%, 81.3%, 96.3%, 100.0% and 96.8%, respectively. We found no significant difference in signal and contrast enhancement appearance among all LR-M categories (p-value =0.34 at Chi square test). However, among LR-M categories the presence of satellite nodules was a feature typical of cHCC-CC (p-value < 0.05 at Chi square test). The presence of intra lesion necrosis and haemorrhage was suggestive of sarcoma (p-value < 0.05 at Chi square test). CONCLUSIONS: High diagnostic accuracy was obtained by LI-RADS classification between malignant and benign lesion. The presence of ancillary features could help the radiologist towards a correct diagnosis.

Supplementation and Performance for Wheelchair Athletes: A Systematic Review.

This systematic review aimed to identify nutritional interventions and supplements that improve the performance for wheelchair athletes. Intervention trials involving high-performance wheelchair athletes were analyzed, including those that comprised a nutritional intervention, defined as any intervention related to food, beverages, and supplementation aiming at evaluating the performance of wheelchair athletes. Of the included studies, four evaluated caffeine supplementation, of which one also evaluated sodium citrate supplementation; two studies evaluated vitamin D supplementation; one study assessed creatine monohydrate supplementation; and one assessed carbohydrate supplementation. Most studies were conducted on athletes with spinal cord injury. Athletes who consumed caffeine exhibited an improvement in performance, but this finding is not strong enough to become a recommendation.

Nimotuzumab for COVID-19: case series.

Background: In COVID-19, EGFR production is upregulated in the alveolar epithelial cells. EGFR overexpression further activates STAT-3 and increases lung pathology. The EGFR pathway is also one of the major nodes in pulmonary fibrosis. Methods: Nimotuzumab, a humanized anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Results: Nimotuzumab was well tolerated. IL-6 decreased from the first antibody infusion. Clinical symptoms significantly improved after nimotuzumab administration, and the CT scans at discharge showed major resolution of the lung lesions and no signs of fibrosis. Conclusion: Safe anti-EGFR antibodies like nimotuzumab may modulate COVID-19-associated hyperinflammation and prevent fibrosis. Clinical Trial Registration: RPCEC00000369 (RPCEC rpcec.sld.cu).

Lay abstract Background: In COVID-19, the protein EGFR is overactive in the infected lung cells. Methods: Nimotuzumab, an anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Results: Nimotuzumab was safe. The most important inflammatory markers decreased from the first administration. The patients' clinical symptoms and imaging results improved significantly. Conclusion: Anti-EGFR antibodies like nimotuzumab may contribute to the recovery of COVID-19 patients without long-term consequences.

Azasteroids from diosgenin: Synthesis and evaluation of their antiproliferative activity.

In this work, we report the synthesis of two new azasteroids through the modification of the A and B rings of diosgenin 1. The 4-azasteroid derivative 12 was prepared in three steps using the α,ß-insaturated-3-keto compound 11 as a precursor, which was first oxidized with KMnO4/KIO4 followed by an oxidative cleavage of ring A, and subsequently cyclized with an ammonium salt, under focused microwave irradiation for a short time of 3 min. A second azasteroid was synthesized, for which the key step was the Beckmann rearrangement of ring B of the oxime 16, affording the lactam-type enamide 17 in good yield. The methodologies developed for the synthesis of the precursors derivatives 10 and 11 contribute to improved yields, compared to those reported in the literature. The biological activity of the azasteroidal compounds 12 and 17 and their precursors has been evaluated in cervical cancer cells (HeLa), colon (HCT-15), and triple negative breast cancer (MDA-MB-231) lines.

Health Care-Associated Infection in Solid Organ Transplant Recipients.

BACKGROUND: Health care-associated infection (HAI) represent a global health problem with an increase in hospital stays, deaths, and monetary costs. Recipients of solid organ transplants are a population at risk. The objectives of the study were to characterize the incidence of HAI in renal and hepatic transplant recipients as well as to compare them with the population without transplants in intensive care units (ICU). METHODS: The data on the incidence of HAI, localization, microorganisms, and demographics were taken from the patients admitted between the years 2013 to 2018 (n = 4307) from the registration of the Project for the Reduction of Nosocomial Infection in Intensive Care Units. The variables were compared with those of renal transplant (n = 96) and liver transplants (n = 68) recipients. RESULTS: Renal transplant recipients showed 26% incidence of HAI. The most frequent were surgical site infection (SSI), urinary tract infection, and primary bacteremia; the most frequent microorganism was Staphylococcus spp, mortality 3.8%. Liver transplant recipients showed 41% incidence of HAI. The most frequent were tracheobronchitis associated with mechanical ventilation, SSI, and primary bacteremia; the most frequent microorganism was Staphylococcus spp, mortality 37%. The population without transplants in the ICU showed 17% incidence of HAI. The most frequent were respiratory infections associated with mechanical ventilation, primary bacteremia, and SSI; the most frequent microorganism was Acinetobacter spp, mortality 21%. CONCLUSIONS: HAI in recipients of solid organ transplants (renal and hepatic) have a higher incidence than in a population without transplants. The location and causal microorganisms have particularities that must be taken into account for the development of prevention protocols.

A semi-automated protocol for NGS metabarcoding and fungal analysis in forensic.

Metabarcoding through Next Generation Sequencing (NGS) has revolutionized environmental biological studies. The availability of this technical approach has opened the opportunity for a systematic implementation of fungal metabarcoding analysis in forensics, where standardized, sensitive and reproducible protocols are highly desirable. In the present paper, a pipeline including a semi-automated molecular protocol and user-friendly bioinformatics tools are applied to several kinds of environmental samples and forensic caseworks. The identification of fungi that characterize specific environments (like Aspergillus for indoor walls, or Penicillium, Debaryomices and Wickerhamomyces for food storage) can be informative for the provenance of samples. In some situations, fungal analysis cannot allow the identification of a defined environment but seems useful to cluster samples with similar provenance. Based on these considerations, fungal analysis can be included in a wider process of non-human DNA identification in order to provide clues on sample provenance.

Coronary Inflammation by Computed Tomography Pericoronary Fat Attenuation in MINOCA and Tako-Tsubo Syndrome.

Background The pericoronary fat attenuation index (pFAI) has emerged as a marker of coronary inflammation, which is measurable from standard coronary computed tomography angiography (CCTA). It compares well with gold-standard methods for the assessment of coronary inflammation and can predict future cardiovascular events. pFAI could prove invaluable to differentiate an inflammatory from a noninflammatory coronary artery status, helping unravel the mechanisms subtending an event classified as myocardial infarction with nonobstructive coronary arteries (MINOCA) or Tako-Tsubo syndrome (TTS). Methods and Results Patients admitted with MINOCA and TTS between 2011 and 2018, who had both CCTA and cardiac magnetic resonance during or shortly after the acute phase, were selected and pFAI measured in their CCTA; pFAI was also measured in control subjects who had CCTA for atypical chest pain workup, no obstructive coronary artery disease found in their CCTA, and no cardiac events at 2-year follow-up. In the n=106 MINOCA/TTS patients, mean pFAI was -68.37±8.29 versus -78.03±6.20 in the n=106 controls (P<0.0001), and the difference was confirmed also when comparing mean pFAI in each coronary artery between MINOCA/TTS and controls (P<0.0001). Nonobstructive coronary plaques at CCTA, high-risk plaques in particular, were more frequently found (P<0.01) in the MINOCA/TTS group compared with controls. Conclusions In MINOCA and TTS patients, CCTA is not only able to detect angiographically invisible atherosclerotic plaques, but its diagnostic yield can be expanded using the simple measurement of pFAI to characterize pericoronary fat tissue; in MINOCA/TTS mean pFAI demonstrates higher values compared with controls, a finding that has been associated with coronary artery inflammation.

Switch From Twice-daily Tacrolimus to Once-daily, Prolonged-release Tacrolimus in Kidney Transplantation: Long-term Outcome.

BACKGROUND: One daily dose of tacrolimus (QDT) improves adherence in kidney transplant (KT) recipients. A switch from twice-daily tacrolimus (BDT) to QDT showed similar efficacy and safety. METHODS: The aim of our study was to demonstrate the long-term efficacy and safety of switching from BDT to QDT in KT recipients. Preliminary results have already been published. Forty-one patients (34 men and 7 women), mean age at KT of 43.9 ± 12.7 years, underwent a 1:1 dose switch from BDT to QDT; the mean time from KT to switch was 36.6 ± 16.1 months. In our study population, 4 patients received a living donor KT and 2 received a second allograft. RESULTS: The mean follow-up was 86.8 ± 13 months from the switch and 126.2 ± 22.3 months from KT. Graft and patient survival rates were 90.2% and 95.1%, respectively. All patients maintained stable renal function during follow-up. During the first 3 months after the switch we observed a significant decrease in tacrolimus blood level (P = .0001). No significant differences were observed regarding tacrolimus dose before and after QDT introduction (P = not significant [NS]). Fourteen patients who stopped steroids under BDT treatment and 16 patients who stopped steroids after the switch are currently steroid-free. CONCLUSION: Our study showed safety and efficacy in switching from BDT to QDT. After early (<1 year) dose adjustment, tacrolimus blood levels remained stable throughout follow-up. Moreover, QDT represented a valid alternative for patients showing steroid side effects.

Muscular Strength Adaptations and Hormonal Responses After Two Different Multiple-Set Protocols of Resistance Training in Postmenopausal Women.

Nunes, PRP, Barcelos, LC, Oliveira, AA, Furlanetto, R, Martins, FM, Resende, EAMR, and Orsatti, FL. Muscular strength adaptations and hormonal responses after two different multiple-set protocols of resistance training in postmenopausal women. J Strength Cond Res 33(5): 1276-1285, 2019-We studied the effects of 2 different resistance training (RT) multiple-set protocols (3 and 6 sets) on muscle strength and basal hormones concentrations in postmenopausal women (PW). Postmenopausal women were randomly allocated into 3 groups: control (CT, n = 12), low RT volume (LV = 3 sets for each exercise, n = 10), and high RT volume (HV = 6 sets for each exercise, n = 12). The LV and HV groups performed 8 exercises of a total body RT protocol 3 times a week, at 70% of 1 repetition maximum (1RM) for 16 weeks. Muscle strength and basal hormone concentrations were measured before and after RT. Our findings show that 3 sets or 6 sets at 70% of 1RM protocol increased muscular strength similarly after 16 weeks (sum of all exercises, LV: 37.7% and HV: 34.1% vs. CT: 2.1%, p < 0.001). Moreover, the RT volume does not affect basal levels of testosterone (TT) (LV: 0.02%, HV: -0.12%, and CT: 0.006%, p = 0.233), cortisol (C) (LV: 72.4%, HV: 36.8%, and CT: 16.8%, p = 0.892), insulin-like growth factor-1 (LV: 6.7%, HV: 7.3%, and CT: 4.1%, p = 0.802), dehydroepiandrosterone sulfate (LV: 0.1%, HV: -4.5%, and CT: -6.7%, p = 0.885), and TT:C ratio (LV: -0.9%, HV: -1.6%, and CT: -0.4%, p = 0.429). Our results suggest that 3 sets and 6 sets at 70% of 1RM seem to promote similar muscle strength gain. Thus, 3-set RT is a time efficient protocol for strength gain after 16 weeks in PW.

Low-intensity resistance training with partial blood flow restriction and high-intensity resistance training induce similar changes in skeletal muscle transcriptome in elderly humans.

We aimed to investigate the mechanisms underlying muscle growth after 12 weeks of resistance training performed with blood flow restriction (RT-BFR) and high-intensity resistance training (HRT) in older individuals. Participants were allocated into the following groups: HRT, RT-BFR, or a control group. High-throughput transcriptome sequencing was performed by the Illumina HiSeq 2500 platform. HRT and RT-BFR presented similar increases in the quadriceps femoris cross-sectional area, and few genes were differently expressed between interventions. The small differences in gene expression between interventions suggest that similar mechanisms may underpin training-induced muscle growth.

Effect of resistance training volume on walking speed performance in postmenopausal women: A randomized controlled trial.

Low muscle strength and high abdominal fatness play an important role in fast and usual walking speeds decrement in postmenopausal women (PW). Low-volume resistance training (RT) improves muscle strength. However, high-volume RT has shown to improve muscle strength and abdominal fatness in PW. Thus, high-volume RT would elicit greater improvement in fast and usual walking speeds than low-volume RT. OBJECTIVE: To confirm whether the high-volume RT is better than the low-volume RT, we performed a randomized controlled trial (clinical trial registration: RBR-8SBBVP) study to investigated the effects of two different RT volumes (three sets vs. six sets) on fast and usual walking speed performances (fast: one-mile walk test and usual: four-meter walk), muscle strength (1RM test), and abdominal fatness (WC - waist circumference; WC/W waist circumference-to-weight ratio; WHtR - waist-to-height ratio; ABSI - A body shape index; BRI - body roundness index; CI - conicity index) in PW. METHODS: Thirty-three PW were randomized (simple randomization) in three groups: control group (CT - no exercise), low-volume RT (LV) and high-volume RT (HV). The RT consisted of eight total body exercises at 70% of one repetition maximum for 16weeks performed three times a week. RESULTS: The fast walking speed (6.1% [CI 95% 2.3-9.9]), WC (-4.1% [CI 95% -6.9 to -1.4]), WHtR (-4.2% [CI 95% -7.0 to -1.4]) and BRI (-10.3% [CI 95% -17.3 to -3.4]) improved in the HV when compared to the LV and CT. The WC/W (-3.7% [CI 95% -6.5 to -0.93]), ABSI (-3.8% [CI 95% -6.5 to -1.2]) and CI (-3.9% [CI 95% -6.6 to -1.3]) improved in the HV when compared to the CT. Muscle strength improved similarly in trained groups (LV: 49.1% [CI 95% 42.5-55.6] and HV: 43.7% [CI 95% 33.0-54.5]) when compared with the CT. No differences were observed in usual walking speed. CONCLUSION: Our results suggest that high-volume RT (six sets) at 70% of 1RM is necessary to promote an improved fast walking speed performance and abdominal fatness in PW.

The Chloroplast Genome of Passiflora edulis (Passifloraceae) Assembled from Long Sequence Reads: Structural Organization and Phylogenomic Studies in Malpighiales.

The family Passifloraceae consists of some 700 species classified in around 16 genera. Almost all its members belong to the genus Passiflora. In Brazil, the yellow passion fruit (Passiflora edulis) is of considerable economic importance, both for juice production and consumption as fresh fruit. The availability of chloroplast genomes (cp genomes) and their sequence comparisons has led to a better understanding of the evolutionary relationships within plant taxa. In this study, we obtained the complete nucleotide sequence of the P. edulis chloroplast genome, the first entirely sequenced in the Passifloraceae family. We determined its structure and organization, and also performed phylogenomic studies on the order Malpighiales and the Fabids clade. The P. edulis chloroplast genome is characterized by the presence of two copies of an inverted repeat sequence (IRA and IRB) of 26,154 bp, each separating a small single copy region of 13,378 bp and a large single copy (LSC) region of 85,720 bp. The annotation resulted in the identification of 105 unique genes, including 30 tRNAs, 4 rRNAs, and 71 protein coding genes. Also, 36 repetitive elements and 85 SSRs (microsatellites) were identified. The structure of the complete cp genome of P. edulis differs from that of other species because of rearrangement events detected by means of a comparison based on 22 members of the Malpighiales. The rearrangements were three inversions of 46,151, 3,765 and 1,631 bp, located in the LSC region. Phylogenomic analysis resulted in strongly supported trees, but this could also be a consequence of the limited taxonomic sampling used. Our results have provided a better understanding of the evolutionary relationships in the Malpighiales and the Fabids, confirming the potential of complete chloroplast genome sequences in inferring evolutionary relationships and the utility of long sequence reads for generating very accurate biological information.

Everolimus and Advagraf Ab Initio in Combined Liver and Kidney Transplant With Donor-Specific Antibodies: A Case Report.

Although donor-specific antibodies are regarded as a contraindication for kidney transplantation, the data available for combined liver and kidney transplantation (cLKTx) are scarce, and there is no established therapeutic approach for this category of transplant recipients. De novo use of everolimus and a reduced dose of calcineurin inhibitor reportedly provides excellent kidney function compared with a standard regimen containing a calcineurin inhibitor. This strategy, however, has been applied in only some recipient categories. Here we report a case of A highly sensitized male patient who underwent a cLKTx and received everolimus with low-dose tacrolimus (once-daily prolonged-release formulation) as ab initio immunosuppressive treatment. The pretransplant panel-reactive antibody estimate was 97%, and multiple anti-HLA antibodies were detected at the time of transplantation. Thus far, patient and allograft survival have reached 2 years, with the recipient remaining on a regimen of immunosuppression with everolimus and low-dose tacrolimus, with no episodes of rejection.

Genome-based study of a spatio-temporal cluster of invasive meningococcal disease due to Neisseria meningitidis serogroup C, clonal complex 11.

OBJECTIVES: To describe a spatio-temporal cluster of invasive meningococcal disease (IMD) due to serogroup C meningococci, occurred in a restricted area of Tuscany between January and October 2015, and the results of whole genome sequencing (WGS). METHODS: Surveillance activities and public health measures were implemented in the Region. Bacterial isolates from IMD cases were characterized by the National Reference Laboratory of the Istituto Superiore di Sanità (ISS), and WGS was performed on available strains. The kSNP software was used to identify core genome SNPs. RESULTS: Overall, 28 IMD cases due to meningococcus C were identified up to 31st October, 2015. Of them, 26 were due to meningococcus C:P1.5-1,10-8: F3-6:ST-11 (cc11) and 2 to C:P1.5-1,10-8: F3-6:ST-2780 (cc11). WGS of 13 meningococci isolated during the outbreak occurred in Tuscany in 2015 showed higher similarity when compared with those of 47 C: P1.5-1,10-8: F3-6:ST-11 (cc11) invasive strains from sporadic cases previously detected in Italy. CONCLUSIONS: A highly aggressive meningococcal C strain was involved in the cluster of severe IMD occurred in Tuscany, a Region with high vaccine coverage among children. Whether this was due to low herd immunity related to the short duration of vaccine protection needs further investigation.

Identification of a novel agrin-dependent pathway in cell signaling and adhesion within the erythroid niche.

Establishment of cell-cell adhesion is crucial in embryonic development as well as within the stem cell niches of an adult. Adhesion between macrophages and erythroblasts is required for the formation of erythroblastic islands, specialized niches where erythroblasts proliferate and differentiate to produce red blood cells throughout life. The Eph family is the largest known family of receptor tyrosine kinases (RTKs) and controls cell adhesion, migration, invasion and morphology by modulating integrin and adhesion molecule activity and by modifying the actin cytoskeleton. Here, we identify the proteoglycan agrin as a novel regulator of Eph receptor signaling and characterize a novel mechanism controlling cell-cell adhesion and red cell development within the erythroid niche. We demonstrate that agrin induces clustering and activation of EphB1 receptors on developing erythroblasts, leading to the activation of α5ß1 integrins. In agreement, agrin knockout mice display severe anemia owing to defective adhesion to macrophages and impaired maturation of erythroid cells. These results position agrin-EphB1 as a novel key signaling couple regulating cell adhesion and erythropoiesis.