Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations

Hemolytic uremic syndrome (HUS) is a disease of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. About 90% of cases are secondary to infections by Escherichia coli strains producing Shiga-like toxins (STEC-HUS), while 10% are associated with mutations in genes encoding proteins of complement system (aHUS). We describe two patients with a clinical history of STEC-HUS, who developed end-stage renal disease (ESRD) soon after disease onset. They received a kidney transplant but lost the graft for HUS recurrence, a complication more commonly observed in aHUS. Before planning a second renal transplantation, the two patients underwent genetic screening for aHUS-associated mutations that revealed the presence of a heterozygous CFI mutation in patient #1 and a heterozygous MCP mutation in patient #2, and also in her mother who donated the kidney. This finding argues that the two cases originally diagnosed as STEC-HUS had indeed aHUS triggered by STEC infection on a genetic background of impaired complement regulation. Complement gene sequencing should be performed before kidney transplantation in patients who developed ESRD following STEC-HUS since they may be undiagnosed cases of aHUS, at risk of posttransplant recurrence. Furthermore, genetic analysis of donors is mandatory before living-related transplantation to exclude carriers of HUS-predisposing mutations. Two patients with a clinical history of D+ hemolytic uremic syndrome associated with Shiga-toxin-producing 0157:H7 E. coli and recurrence in the kidney graft carry heterozygous mutations in the genes encoding complement factor I (patient 1) and membrane cofactor protein (patient 2). © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons

A fully automatic forest parameters extraction at single-tree level: a comparison of MLS and TLS applications

Forests are vital for ecological, economic, and social reasons, and adopting sustainable forest management practices is necessary. While traditional forest monitoring techniques provide detailed data, they are time-consuming; conversely, geomatic techniques can provide more detailed data for forest resource management. This study aims to assess the suitability of Mobile Mapping Systems (MMS) with simultaneous localisation and mapping (SLAM) technology for precision forestry purposes in challenging environments. We compared the performance of MMS data with Terrestrial Laser Scanning (TLS) data and evaluated the Forest Structural Complexity Tool (FSCT), which was developed for TLS datasets, on MMS data. The case study area is a highly sloped coniferous forest in the Italian Alps affected by a severe fire in 2017. Data were processed using a fully automated open-source Python tool that detects each tree's position, Diameter at Breast Height (DBH), and height. The validation procedure was conducted with respect to the TLS point cloud manually segmented. The results show that using MMS with SLAM technology is suitable for precision forestry purposes in challenging environments and that FSCT performs well on MMS data

Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV

Genetic research: the role of citizens, public health and international stakeholders

Background: Genetic research has become an indispensable instrument for medical research, and the subjects involved have both divergent and convergent interests. Objective: The possibility of having more detailed genetic information undoubtedly offers benefits for the health of the subject, but could also pose risks and make the subject vulnerable to discrimination. Methods: The scientific community has viewed very favorably the public health utility of family history, in which data from a family whose members suffer from chronic pathologies is collected and filed, in order to develop a sort of “stratification of family risk.” Even though in the last decade the scientific and juridical literature has contributed greatly to the topic of biobanks, the perplexities that continue to surround this theme give the idea that current ethical protocols on research are inadequate. Results: Researchers, citizens, International stakeholders, mass media, Public Health and Governments play a key role in genetic research. It is obvious that the methods used for genetic research do not present intrinsic risks; they are much less dangerous than other activities of diagnosis and research. Before authorizing a research project, it is important to reflect on the responsibility and transparency of the studies to be conducted, and on the impact they may have on the interests of public health. Conclusion: We believe that the highest priority need is to develop a common language on the theme, as is the case in the sphere of clinical experimentation where rules of good clinical practice, albeit at times conflicting, have led to uniform convergences in the scientific world on the points to be actuated

Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study

Introduction: Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. the aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV).Methods: A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality.Results: A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P=0.001) despite similar PaO2/FiO(2) ratios and acute respiratory distress syndrome (ARDS) severity. in a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% Cl, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; Cl 95%, 1.00 to 1.04), severe ARDS (OR 1.44; Cl 95%, 1.09 to 1.91) and deep sedation (OR 2.36; Cl 9596, 1.31 to 4.25) were independently associated with increased hospital mortality.Conclusions: Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients.Research and Education Institute from Hospital Sirio-Libanes, São PauloD'Or Institute for Research and Education, Rio de Janeiro, BrazilBrazilian Research in Intensive Care NetworkHosp Copa DOr, BR-22031010 Rio de Janeiro, BrazilHosp Sirio Libanes, Res & Educ Inst, BR-01308060 São Paulo, BrazilUniv São Paulo, Fac Med, Hosp Clin, ICU,Emergency Med Dept, BR-05403000 São Paulo, BrazilHosp Sao Camilo Pompeia, ICU, BR-05022000 São Paulo, BrazilCEPETI, BR-82530200 Curitiba, Parana, BrazilHosp Canc I, Inst Nacl Canc, ICU, BR-20230130 Rio de Janeiro, BrazilPasteur Hosp, ICU, BR-20735040 Rio de Janeiro, BrazilIrmandade Santa Casa Misericordia Porto Alegre, RIPIMI, BR-90020090 Porto Alegre, RS, BrazilVitoria Apart Hosp, ICU, BR-29161900 Serra, ES, BrazilHosp Mater Dei, ICU, BR-30140093 Belo Horizonte, MG, BrazilHosp Santa Luzia, ICU, BR-70390902 Brasilia, DF, BrazilHosp Sao Luiz, ICU, BR-04544000 São Paulo, BrazilUniversidade Federal de São Paulo, Anesthesiol Pain & Intens Care Dept, ICU, BR-04024900 São Paulo, BrazilHosp Sao Jose Criciuma, ICU, BR-88801250 Criciuma, BrazilUDI Hosp, ICU, BR-65076820 Sao Luis, BrazilUniv São Paulo, Univ Hosp, ICU, BR-05508000 São Paulo, BrazilUniv São Paulo, Fac Med, Hosp Clin, ICU,Surg Emergency Dept, BR-05403000 São Paulo, BrazilIDOR DOr Inst Res & Educ, BR-22281100 Rio de Janeiro, BrazilInst Nacl Canc, Postgrad Program, BR-20230130 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Anesthesiol Pain & Intens Care Dept, ICU, BR-04024900 São Paulo, BrazilWeb of Scienc

Adherence to Mediterranean Diet and Diet Quality in Patients with Inflammatory Bowel Disease: A Single-Center, Observational, Case-Control Study

The nutritional status in inflammatory bowel disease (IBD) is often impaired, and adherence to the Mediterranean diet (MedDiet) remains under-investigated. The aim of this study was to assess diet quality (DQ) and adherence to MedDiet in a cohort of Sardinian IBD patients. We conducted a case-control study in which 50 Crohn's disease (CD) and 50 ulcerative colitis (UC) patients were matched with 100 healthy controls each. The Diet Quality Index (DQI-I) and Medi-Lite were used to assess DQ and adherence to MedDiet, respectively. Subgroup analysis by disease characteristics and use of advanced therapies were also carried out. DQI-I scored significantly lower in IBD, independently of disease localization and behavior (CD) and disease extent (UC): [DQI-I: CD 34.5 (IQR 33-37) vs. CTRL 40 (IQR 38.5-43) p < 0.0001; UC 34.5 (IQR 33-37) vs. CTRL 42 (IQR 40-44) p < 0.0001]. Medi-Lite scores were significantly lower in stricturing and ileo-colonic CD and in extensive UC: [Medi-Lite CD 7.5 (IQR 7-9)] vs. CTRL 9 (IQR 7-10) p = 0.0379]; [UC 8 (IQR7-10) vs. CTRL 9 (IQR 8-10.5) p = 0.0046]. IBD patients had a low DQ independently of disease type and phenotype. Patients with ileo-colonic stenosing CD or extensive UC had lower MedDiet adherence, suggesting that its benefits may be mitigated by low acceptance in specific subgroups

Therapeutic Strategies and Genetic Implications for Periodontal Disease Management: A Systematic Review

The objective of this review is to identify the microbiological alterations caused by various therapy modalities by critically analyzing the current findings. We limited our search to English-language papers published between 1 January 2004 and 7 May 2024 in PubMed, Scopus, and Web of Science that were relevant to our topic. In the search approach, the Boolean keywords “microbio*” AND “periodontitis” were used. A total of 5152 papers were obtained from the databases Web of Science (2205), PubMed (1793), and Scopus (1154). This resulted in 3266 articles after eliminating duplicates (1886), and 1411 entries were eliminated after their titles and abstracts were examined. The qualitative analysis of the 22 final articles is included in this study. Research on periodontal disease shows that periodontitis alters the oral microbiome and increases antibiotic resistance. Treatments like scaling and root planing (SRP), especially when combined with minocycline, improve clinical outcomes by reducing harmful bacteria. Comprehensive mechanical debridement with antibiotics, probiotics, EMD with bone grafts, and other adjunctive therapies enhances periodontal health. Personalized treatment strategies and advanced microbial analyses are crucial for effective periodontal management and antibiotic resistance control

A Remote Monitoring System to Optimize the Home Management of Oral Anticancer Therapies (ONCO-TreC): Prospective Training-Validation Trial

Background: A platform designed to support the home management of oral anticancer treatments and provide a secure web-based patient–health care professional communication modality, ONCO-TreC, was tested in 3 cancer centers in Italy. Objective: The overall aims of the trial are to customize the platform; assess the system’s ability to facilitate the shared management of oral anticancer therapies by patients and health professionals; and evaluate system usability and acceptability by patients, caregivers, and health care professionals. Methods: Patients aged ≥18 years who were candidates for oral anticancer treatment as monotherapy with an Eastern Cooperative Oncology Group performance status score of 0 to 1 and a sufficient level of familiarity with mobile devices were eligible. ONCO-TreC consisted of a mobile app for patients and a web-based dashboard for health care professionals. Adherence to treatment (pill count) and toxicities reported by patients through the app were compared with those reported by physicians in medical records. Usability and acceptability were evaluated using questionnaires. Results: A total of 40 patients were enrolled, 38 (95%) of whom were evaluable for adherence to treatment. The ability of the system to measure adherence to treatment was high, with a concordance of 97.3% (95% CI 86.1%-99.9%) between the investigator and system pill count. Only 60% (3/5) of grade 3, 54% (13/24) of grade 2, and 19% (7/36) of grade 1 adverse events reported by physicians in the case report forms were also reported in the app directly by patients. In total, 94% (33/35) of patients had ≥1 app launch each week, and the median number of daily accesses per patient was 2. Approximately 71% (27/38) and 68% (26/38) of patients used the app for messages and vital sign entering, respectively, at least once during the study period. Conclusions: ONCO-TreC is an important tool for measuring and monitoring adherence to oral anticancer drugs. System usability and acceptability were very high, whereas its reliability in registering toxicity could be improved

Two novel PRNP truncating mutations broaden the spectrum of prion amyloidosis

Truncating mutations in PRNP have been associated with heterogeneous phenotypes ranging from chronic diarrhea and neuropathy to dementia, either rapidly or slowly progressive. We identified novel PRNP stop-codon mutations (p.Y163X, p.Y169X) in two Italian kindreds. Disease typically presented in the third or fourth decade with progressive autonomic failure and diarrhea. Moreover, one proband (p.Y163X) developed late cognitive decline, whereas some of his relatives presented with isolated cognitive and psychiatric symptoms. Our results strengthen the link between PRNP truncating mutations and systemic abnormal PrP deposition and support a wider application of PRNP screening to include unsolved cases of familial autonomic neuropathy