Structural and biochemical insights of CypA and AIF interaction

The Cyclophilin A (CypA)/Apoptosis Inducing Factor (AIF) complex is implicated in the DNA degradation in response to various cellular stress conditions, such as oxidative stress, cerebral hypoxia-ischemia and traumatic brain injury. The pro-apoptotic form of AIF (AIF(Δ1-121)) mainly interacts with CypA through the amino acid region 370-394. The AIF(370-394) synthetic peptide inhibits complex formation in vitro by binding to CypA and exerts neuroprotection in a model of glutamate-mediated oxidative stress. Here, the binding site of AIF(Δ1-121) and AIF(370-394) on CypA has been mapped by NMR spectroscopy and biochemical studies, and a molecular model of the complex has been proposed. We show that AIF(370-394) interacts with CypA on the same surface recognized by AIF(Δ1-121) protein and that the region is very close to the CypA catalytic pocket. Such region partially overlaps with the binding site of cyclosporin A (CsA), the strongest catalytic inhibitor of CypA. Our data point toward distinct CypA structural determinants governing the inhibitor selectivity and the differential biological effects of AIF and CsA, and provide new structural insights for designing CypA/AIF selective inhibitors with therapeutic relevance in neurodegenerative diseases

Making forest monitoring cheaper and closer to society: The LIFE+ Project "SMART4Action"

LIFE SMART4Action (Sustainable Monitoring And Reporting To Inform Forest- and. Environmental Awareness and Protection. LIFE13 ENV/IT/000813) intends to redesign forest monitoring and its information and reporting system in Italy. It is designed over the period September 2014 - March 2018 and will attempt to ensure financial sustainability to forest monitoring, despite budget restrictions, whilst maintaining scientific reliability. The project has two main goals: . design a new system to reduce the current annual costs by 30%, while recognizing the importance of national and regional statistics on key variables linked to sustainable forest management and ecosystem services; and . to improve communication with, and data transfer to, relevant stakeholders and citizens through a participatory process. The analysis of the available data series of forest monitoring data will permit to optimize the number of plots, the frequency and the distribution of the activities, to maximize the information, and identify possible areas were monitoring and modeling can be fruitfully integrated. To increase awareness about forest related issues and the importance of forest monitoring, SMART4Action will develop mechanisms to involve local people in plot management and basic monitoring for readily measurable variables, with local conferences and courses, synthetic result sheets at regional scale, and web-based and smartphone applications to obtain an active involvement of citizens. Present and historical monitoring data will also be shared online using geospatial standard services. Here, we intend to present the project at its very beginning in order to explore the possibility of interaction and synergy with other on-going activities

Role of the ENPP1 K121Q Polymorphism in Glucose Homeostasis

OBJECTIVE— To study the role of the ENPP1 Q121 variant on glucose homeostasis in whites from Italy

Surgical management of pediatric vesicoureteral reflux: A comparative study between endoscopic, laparoscopic, and open surgery

Our retrospective study compared the results of three surgical procedures for correction of pediatric vesicoureteral reflux (VUR): open Cohen, laparoscopic Lich-Gregoir reimplantation (LEVUR), and endoscopic subureteric injection (STING) procedure. METHODS: We analyzed 90 patients (50 girls, 40 boys, average age 4.86 years) operated in two centers of pediatric surgery for VUR. Exclusion criteria were Grade 1 VUR, Grade 5 VUR with megaureters requiring ureteral tapering, secondary VUR, and patients already operated for VUR. Thirty patients underwent Cohen, 30 LEVUR, and 30 STING procedure. Follow-up included renal ultrasonography and voiding cystourethrography 6 months postoperatively. The statistical analysis was performed using χ(2) Pearson and Fisher tests. RESULTS: Operative time was shorter using STING either for unilateral or bilateral correction (P = .001). Hospitalization was statistically shorter using STING and LEVUR compared to Cohen (P = .001). The pain scores were worse after Cohen (P = .001). Analgesic requirements were higher after Cohen (P = .001). Reflux persistence was higher after STING (10 cases versus 5 Cohen and 4 LEVUR). Cohen presented more complications compared to LEVUR and STING (P = .001). Intraoperative costs were higher for STING procedure (P = .001), while hospitalization costs were significantly higher for Cohen procedure (P = .001). CONCLUSIONS: In children affected by VUR, open Cohen and LEVUR reported a higher success rate than STING procedure. However, Cohen procedure had a very long and painful hospital stay, more complications, more analgesic requirements compared to STING and LEVUR. Comparing the three techniques, it seems that LEVUR presents a high success rate similar to the Cohen procedure, but in addition, it presents the same advantages of STING procedure with no postoperative pain and a lower postoperative morbidity

Chemical vs. Enzymatic refining to produce peanut oil for edible use or to obtain a sustainable and cost-effective protector for stored grains against Sitophilus zeamais (Coleoptera: Curculionidae)

Among the various existing techniques, enzymatic degumming represents a process that is establishing itself as a valid alternative to the more classic chemical processes. Moreover, vegetable oils of various origins have been gaining more consideration as sustainable and affordable protectants for cereals and pulses against the attack of several insect pests. Sitophilus zeamais (Motschulsky) (Coleoptera: Curculionidae) is one of the key pests of cereal crops in the field and in stored and processed cereal products. Based on these highlighted issues, the overall aim of this research was twofold: (i) firstly, the effectiveness of the enzymatic degumming process was evaluated through the use of three different enzymes in order to verify the possible industrial application within the SALOV company as an alternative to the conventional chemical process; (ii) in a second phase, the possible use of the innovative refined oils was explored for sustainable stored grain protection towards S. zeamais. The results obtained confirm the strong possibility of applying the enzymatic process, which is innovative and, in a chemical way, more sustainable than the classical one. Regarding the toxicity towards S. zeamais, the crude peanut oil and the chemically refined peanut oil had lower LC50 values (1.836 and 1.372 g kg-1, respectively) than the oils rectified through enzymatic degumming (LC50 from 2.453 to 4.076 g kg-1), and, therefore, they can be suggested as sustainable stored grain protectants

Laparoscopic transposition of lower pole crossing vessels (vascular hitch) in children with pelviureteric junction obstruction

Abstract BACKGROUND: Congenital hydronephrosis due to intrinsic or extrinsic uretero-pelvic-junction (UPJ) obstruction (UPJO) is a common problem in childhood UPJO may be caused by intrinsic disorganization or by extrinsic compression from crossing vessels (CV); extrinsic causes usually present symptomatically in older children. This report the large Italian experience in the treatment of children with extrinsic-UPJO by CV. METHODS: We analyzed the data of 51 children (17 girls and 34 boys, median age 10, 7 years) affected by extrinsic-UPJO were treated in three Italian institutions with laparoscopic transposition of CV (Hellström Vascular Hitch modified by Chapman).The intraoperative diuretic-test was performed in all patients before and after the vessels transpositions confirming the extrinsic-UPJO. We included in the study only patients with suspicion of vascular extrinsic obstruction of the UPJ. Symptoms at presentation were recurrent abdominal/flank pain and haematuria. All patients presented intermittent ultrasound (US) detection of hydronephrosis (range, 18-100 mm). Preoperative diagnostic studies included: US/doppler scan, MAG3-renogram, functional-magnetic-resonance-urography (fMRU). RESULTS: Median operative time was 108 minutes; median hospital stay: 3, 4 days. Unique complications: a small abdominal wall hematoma and higher junction-translocation without obstruction. During follow-up (range, 12-96 months) all patients reported resolution of their symptoms, a decrease in the hydronephrosis grade and improved drainage on diuretic renogram. CONCLUSIONS: We believe that Vascular Hitch is less technically demanding than laparoscopic pyeloplasty, resulting in a lower complication rate and a significantly reduced hospitalization. The results of our study allow us to conclude that laparoscopic VH may be a safe, feasible, and attractive alternative to treat obstructed hydronephrosis due to CV presenting a useful alternative to AHDP in the management of symptomatic children where CV are deemed the sole aetiology. We recommend careful patient selection based on preoperative clinical and radiologic findings that are diagnostic of extrinsic-UPJO, combined with intraoperative-DT to confirm the appropriate selection of corrective procedure

Effectiveness of vaccination against SARS-CoV-2 Omicron variant infection, symptomatic disease, and hospitalization: a systematic review and meta-analysis

Background This meta-analysis aims to assess the effectiveness of the current Sars-Cov2 vaccine regimens against Omicron infection. A secondary endpoint aims to investigate the waning effectiveness of primary vaccination against symptomatic infection and related hospitalization. Research design and methods The systematic review started on 1 December 2021 and was concluded on 1 March 2022. Random-effects frequentist meta-analyses and multiple meta-regressions were performed. Results In total, 15 studies are included in the quantitative synthesis. According to the meta-analysis results, the overall risk of Sars-Cov2 infection in vaccinated individuals is on average 31 center dot 5% lower than the infection risk in unvaccinated while vaccinated with one booster dose have a 70 center dot 4% risk reduction of Omicron infection compared to unvaccinated. In particular, one booster dose significantly decreases by 69% the risk of symptomatic Omicron infection with respect to unvaccinated. Six months after the primary vaccination, the average risk reduction declines to 22% against symptomatic infection and to 55% against hospitalization. Conclusions Primary vaccination does not provide sufficient protection against symptomatic Omicron infection. Although the effectiveness of the primary vaccination against hospitalization due to Omicron remains significantly above 50% after 3 months, it dramatically fades after 6 months

Retroperitoneal and laparoscopic heminephrectomy in duplex kidney in infants and children

Abstract BACKGROUND: Two main techniques are adopted to perform partial nephrectomy in children: laparoscopy and retroperitoneoscopy. The aim of this paper is to review the larger multicentric experience recently published by our group to review indications, techniques and results of both approaches. METHODS: Data of 102 patients underwent partial nephrectomy in a 5-year period using minimally invasive surgery (MIS) procedures were analyzed. Fifty-two children underwent laparoscopic partial nephrectomy (LPN), and 50 children underwent retroperitoneoscopic partial nephrectomy (RPN). Median age at surgery was 4.2 years. Statistical analysis was performed using χ2 test and Student's t-test. RESULTS: The overall complications rate was significantly higher after RPN (15/50, 30%) than after LPN (10/52, 19%) (χ2 =0.05). In LPN group, complications [4 urinomas, 2 symptomatic refluxing distal ureteral stump (RDUS) and 4 urinary leakages] were conservatively managed. In RPN group, complications (6 urinomas, 8 RDUS, 1 opening of remaining calyxes) required a re-operation in 2 patients. In both groups no conversion to open surgery was reported. Operative time (LPN: 166.2 min vs. RPN: 255 min; P<0.001) and hospitalization (LPN: 3.5 days vs. RPN: 4.1 days; P<0.001) were significantly shorter in LPN group. No postoperative loss of renal function was reported in both groups. CONCLUSIONS: MIS now represents the gold standard technique to perform partial nephrectomy in children with duplex kidney. Our results demonstrate that RPN remains a technically demanding procedure with a significantly higher complications and re-operation rate compared to LPN. In addition, length of surgery and hospitalization were significantly shorter after LPN compared to RPN. LPN seems to be a faster, safer and technically easier procedure to perform in children compared to RPN due to a larger operative space and the possibility to perform a complete ureterectomy in refluxing systems

Genotype–phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition. Within this spectrum, patients who meet specific LFS criteria are diagnosed with LFS, while patients who do not meet these criteria are diagnosed with attenuated LFS. To explore genotype–phenotype correlations we analyzed 141 individuals from 94 families with pathogenic TP53 variants registered in the German Cancer Predisposition Syndrome Registry. Twenty-one (22%) families had attenuated LFS and 73 (78%) families met the criteria of LFS. NULL variants occurred in 32 (44%) families with LFS and in two (9.5%) families with attenuated LFS (P value < 0.01). Kato partially functional variants were present in 10 out of 53 (19%) families without childhood cancer except adrenocortical carcinoma (ACC) versus 0 out of 41 families with childhood cancer other than ACC alone (P value < 0.01). Our study suggests genotype–phenotype correlations encouraging further analyses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-022-01332-1