Disability and inclusion: swimming to overcome social barriers

Nowadays all people can and must practice physical activity and engage themselves in various sports specialties. Among the various sports, swimming is ideal in all situations where the weight of the body is a problem, such as in cases of lower limbs disability (amputations, paralysis, etc.). The objective of this study is to investigate if disabled and not-disabled athletes can derive performance benefits and if it is possible to reduce the gap between the competition times between athletes, through a single, performance and training activity. The sample is made up of 12 athletes, including 6 disabled, belonging to the S2 category, and 6 not-disabled athletes skilled in the back. After an anamnesis and a careful initial valuation, it was proposed to all the athletes to do the HIIT method (for 4 weeks), Tabata method (for 4 weeks), and Pilates one (for 8 weeks). Moreover, to the disabled athletes were given physiotherapy sessions to increase joint ROM for 8 weeks. The aim is to promote social inclusion for disabled athletes, often marginalized by the group, to break down those who are the pillars of difference

Tumour-induced osteomalacia: 18 months of 2-weekly burosumab treatment

Summary: Tumour-induced osteomalacia (TIO) is due to an overproduction of fibroblast growth factor 23 (FGF23) by mesenchymal tumours, causing hypophosphatemia, osteomalacia and muscle weakness. TIO is usually cured by tumour resection, but neoplasms may be unidentifiable and unresectable or the patient may refuse surgery. In these cases, medical treatment with oral phosphate and calcitriol is mandatory, but it is not fully effective and it is associated with low compliance. Burosumab, a human MAB against FGF23 employed to treat X-linked hypophosphatemia (XLH), has recently been approved for TIO in the USA. Maximum burosumab dose in XLH is 90 mg administered for 2 weeks; there are no data on clinical efficacy and safety of this dose in TIO. We reported the case of a 73 years old male with multiple non-traumatic fractures, low bone mineral density, pain and reduced independence of activities of daily living. Biochemical evaluation showed hypophosphatemia, high alkaline phosphatase (ALP) and C-terminal telopeptide (CTX) and normal albumin-corrected total calcium and parathyroid hormone. Tubular phosphate reabsorption was low (80%), whereas C-terminal tail of FGF23 (cFGF23) was elevated. A 68Ga-DOTATOC PET was performed, identifying a lesion in the first left rib. The patient refused surgery; therefore, burosumab therapy was started. After 18 months of treatment (maximum dose: 60 mg administered for 2 weeks), plasma phosphate normalized and ALP levels improved (138 U/L). Patient clinical symptoms as well as pain severity and fatigue improved. Neither adverse events nor tumour progression was reported during follow-up except for a painless fracture of the second right rib. Learning points: Our case shows efficacy and safety of burosumab treatment administered every 2 weeks in a tumour-induced osteomalacia (TIO) patient. After 18 months of treatment at a maximum dose of 60 mg every 2 weeks, we found plasma phosphate normalization and ALP reduction as well as improvement in clinical symptoms and fatigue. Neither adverse events nor tumour progression was reported during follow-up, except for a painless fracture of the second right rib

From Ivacaftor to Triple Combination: A Systematic Review of Efficacy and Safety of CFTR Modulators in People with Cystic Fibrosis

Over the last years CFTR (cystic fibrosis transmembrane conductance regulator) modulators have shown the ability to improve relevant clinical outcomes in patients with cystic fibrosis (CF). This review aims at a systematic research of the current evidence on efficacy and tolerability of CFTR modulators for different genetic subsets of patients with CF. Two investigators independently performed the search on PubMed and included phase 2 and 3 clinical trials published in the study period 1 January 2005\u201331 January 2020. A final pool of 23 papers was included in the systematic review for a total of 4219 patients. For each paper data of interest were extracted and reported in table. In terms of lung function, patients who had the most beneficial effects from CFTR modulation were those patients with one gating mutation receiving IVA (ivacaftor) and patients with p.Phe508del mutation, both homozygous and heterozygous, receiving ELX/TEZ/IVA (elexacaftor/tezacaftor/ivacaftor) had the most relevant beneficial effects in term of lung function, pulmonary exacerbation decrease, and symptom improvement. CFTR modulators showed an overall favorable safety profile. Next steps should aim to systematize our comprehension of scientific data of efficacy and safety coming from real life observational studie

Phenotypic and Molecular Selection of a Superior Solanum pennellii Introgression Sub-Line Suitable for Improving Quality Traits of Cultivated Tomatoes

The Solanum pennellii Introgression Line (IL) population can be exploited to identify favorable alleles that can improve yield and fruit quality traits in commercial tomato varieties. Over the past few years, we have selected ILs that exhibit increased content of antioxidant compounds in the fruit compared to the cultivar M82, which represents the genetic background in which the different wild regions of the S. pennellii ILs were included. Recently, we have identified seven sub-lines of the IL7-3 accumulating different amounts of antioxidants in the ripe fruit. Since the wild region carried on chromosome 7 induces a low fruit production in IL7-3, the first aim of the present work was to evaluate yield performances of the selected sub-lines in three experimental fields located in the South of Italy. Another aim was to confirm in the same lines the high levels of antioxidants and evaluate other fruit quality traits. On red ripe fruit, the levels of soluble solids content, firmness, and ascorbic acid (AsA) were highly variable among the sub-lines grown in three environmental conditions, evidencing a significant genotype by environment interaction for soluble solids and AsA content. Only one sub-line (coded R182) exhibited a significantly higher firmness, even though no differences were observed for this trait between the parental lines M82 and IL7-3. The same sub-line showed significantly higher AsA content compared to M82, thus resembling IL7-3. Even though IL7-3 always exhibited a significantly lower yield, all the sub-lines showed yield variability over the three trials. Interestingly, the sub-line R182, selected for its better performances in terms of fruit quality, in all the trials showed a production comparable to that of the control line M82. A group of species-specific molecular markers was tested on R182 and on the parental genotypes in order to better define the wild genomic regions carried by the elite line R182. In these regions three candidate genes that could increase the level of AsA in the fruit were identified. In the future, the line R182 could be used as pre-breeding material in order to obtain new varieties improved for nutritional traits

Gonadotrophin-mediated miRNA expression in testis at onset of puberty in rhesus monkey: Predictions on regulation of thyroid hormone activity and DLK1-DIO3 locus

Molecular mechanisms responsible for the initiation of primate spermatogenesis remain poorly characterized. Previously, 48 h stimulation of the testes of three juvenile rhesus monkeys with pulsatile LH and FSH resulted in down-regulation of a cohort of genes recognized to favor spermatogonia stem cell renewal. This change in genetic landscape occurred in concert with amplification of Sertoli cell proliferation and the commitment of undifferentiated spermatogonia to differentiate. In this report, the non-protein coding small RNA transcriptomes of the same testes were characterized using RNA sequencing: 537 mature micro-RNAs (miRNAs), 322 small nucleolar RNAs (snoRNAs) and 49 small nuclear RNAs (snRNAs) were identified. Pathway analysis of the 20 most highly expressed miRNAs suggested that these transcripts contribute to limiting the proliferation of the primate Sertoli cell during juvenile development. Gonadotrophin treatment resulted in differential expression of 35 miRNAs, 12 snoRNAs and four snRNA transcripts. Ten differentially expressed miRNAs were derived from the imprinted delta-like homolog 1-iodothyronine deiodinase 3 (DLK1-DIO3) locus that is linked to stem cell fate decisions. Four gonadotrophin-regulated expressed miRNAs were predicted to trigger a local increase in thyroid hormone activity within the juvenile testis. The latter finding leads us to predict that, in primates, a gonadotrophin-induced selective increase in testicular thyroid hormone activity, together with the established increase in androgen levels, at the onset of puberty is necessary for the normal timing of Sertoli cell maturation, and therefore initiation of spermatogenesis. Further examination of this hypothesis requires that peripubertal changes in thyroid hormone activity of the testis of a representative higher primate be determined empirically.Fil: Aliberti, Paula. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Endocrinología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sethi, Rahil. University of Pittsburgh; Estados UnidosFil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Endocrinología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chandran, Uma R.. University of Pittsburgh; Estados UnidosFil: Plant, Tony M.. University of Pittsburgh; Estados UnidosFil: Walker, William H.. University of Pittsburgh; Estados Unido

Tailoring CD19xCD3-DART exposure enhances T-cells to eradication of B-cell neoplasms.

Many patients with B-cell malignancies can be successfully treated, although tumor eradication is rarely achieved. T-cell-directed killing of tumor cells using engineered T-cells or bispecific antibodies is a promising approach for the treatment of hematologic malignancies. We investigated the efficacy of CD19xCD3 DART bispecific antibody in a broad panel of human primary B-cell malignancies. The CD19xCD3 DART identified 2 distinct subsets of patients, in which the neoplastic lymphocytes were eliminated with rapid or slow kinetics. Delayed responses were always overcome by a prolonged or repeated DART exposure. Both CD4 and CD8 effector cytotoxic cells were generated, and DART-mediated killing of CD4+ cells into cytotoxic effectors required the presence of CD8+ cells. Serial exposures to DART led to the exponential expansion of CD4 + and CD8 + cells and to the sequential ablation of neoplastic cells in absence of a PD-L1-mediated exhaustion. Lastly, patient-derived neoplastic B-cells (B-Acute Lymphoblast Leukemia and Diffuse Large B Cell Lymphoma) could be proficiently eradicated in a xenograft mouse model by DART-armed cytokine induced killer (CIK) cells. Collectively, patient tailored DART exposures can result in the effective elimination of CD19 positive leukemia and B-cell lymphoma and the association of bispecific antibodies with unmatched CIK cells represents an effective modality for the treatment of CD19 positive leukemia/lymphoma

Amplitude analysis and branching-fraction measurement of Ds+ → π + π 0 η′

Using data collected with the BESIII detector in e+e− collisions at center-of-mass energies between 4.178 and 4.226 GeV and corresponding to 6.32 fb−1 of integrated luminosity, we report the amplitude analysis and branching-fraction measurement of the Ds+→ π+π0η′ decay. We find that the dominant intermediate process is Ds+→ ρ+η′ and the significances of other resonant and nonresonant processes are all less than 3σ. The upper limits on the branching fractions of S-wave and P-wave nonresonant components are set to 0.10% and 0.74% at the 90% confidence level, respectively. In addition, the branching fraction of the Ds+→ π+π0η′ decay is measured to be (6.15 ± 0.25(stat.) ± 0.18(syst.))%, which receives significant contribution only from Ds+→ ρ+η′ according to the amplitude analysis. [Figure not available: see fulltext.]. © 2022, The Author(s)

Metabolomic profiling of food matrices: Preliminary identification of potential markers of microbial contamination

The research aimed to generate an early warning system highlighting in real-time bacterial contamination of meat matrices and providing information which could support companies in accepting or rejecting batches. Current microorganisms’ detection methods rely on techniques (plate counting), which provide retrospective values for microbial contamination. The purpose of this research was to evaluate the ability of the headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC/MS) methodologies to detect volatile organic carbons (VOCs), which may be associated to a peculiar microbiological contamination of food. The disposal of fast headspace gas chromatography-mass spectrometry (HS-SPME-GC/MS) able to accurately and rapidly (30 min per sample) detect pathogens in raw meat could replace the traditional and time-consuming (3 to 4 days) standardized microbiological analysis required by regulations. Experiments focused on qualitative and quantitative evaluations of VOCs produced by Salmonella Typhimurium, Campylobacter jejuni, and Staphylococcus aureus in different types of raw meat (beef, pork, chicken). HS-SPME-GC/MS allowed to use smaller sample volumes compared to traditional methods with no sample processing and the potentiality for its application on various food matrices for the detection of a wide variety of pathogens. Data analysis showed the identification of unique VOCs’ profiles being possible markers of meat contamination due to their association to specific pathogens. The identification of VOCs markers in association to selected bacterial pathogens and their metabolites could support the rapid determination of specific meat samples contamination. Further research is required to outline-specific metabolic profiles for each microorganism responsible of meat contamination and prevent false positives