Yellow Fever Virus Maintained by Sabethes Mosquitoes during the Dry Season in Cerrado, a Semiarid Region of Brazil, in 2021.

In recent decades, waves of yellow fever virus (YFV) from the Amazon Rainforest have spread and caused outbreaks in other regions of Brazil, including the Cerrado, a savannah-like biome through which YFV usually moves before arriving at the Atlantic Forest. To identify the vectors involved in the maintenance of the virus in semiarid environments, an entomological survey was conducted after confirmation of yellow fever (YF) epizootics at the peak of the dry season in the Cerrado areas of the state of Minas Gerais. In total, 917 mosquitoes from 13 taxa were collected and tested for the presence of YFV. Interestingly, mosquitoes of the Sabethes genus represented 95% of the diurnal captured specimens, displaying a peak of biting activity never previously recorded, between 4:30 and 5:30 p.m. Molecular analysis identified three YFV-positive pools, two from Sabethes chloropterus-from which near-complete genomes were generated-and one from Sa. albiprivus, whose low viral load prevented sequencing. Sa. chloropterus was considered the primary vector due to the high number of copies of YFV RNA and the high relative abundance detected. Its bionomic characteristics allow its survival in dry places and dry time periods. For the first time in Brazil, Sa. albiprivus was found to be naturally infected with YFV and may have played a role as a secondary vector. Despite its high relative abundance, fewer copies of viral RNA were found, as well as a lower Minimum Infection Rate (MIR). Genomic and phylogeographic analysis showed that the virus clustered in the sub-lineage YFVPA-MG, which circulated in Pará in 2017 and then spread into other regions of the country. The results reported here contribute to the understanding of the epidemiology and mechanisms of YFV dispersion and maintenance, especially in adverse weather conditions. The intense viral circulation, even outside the seasonal period, increases the importance of surveillance and YFV vaccination to protect human populations in affected areas.

Prognosis of patients with acute lymphoblastic leukaemia relapsing after allogeneic stem cell transplantation.

The outcomes of patients with acute lymphoblastic leukaemia (ALL) presenting relapse after allogeneic stem cell transplant (allo-SCT) are poor, with few data available in this setting. OBJECTIVE AND METHODS: To evaluate the outcomes of patients with ALL presenting relapsed after allo-SCT, we performed a retrospective study including 132 from 11 centres in Spain. RESULTS: Therapeutic strategies consisted of palliative treatment (n = 22), chemotherapy (n = 82), tyrosine kinase inhibitors (n = 26), immunotherapy with inotuzumab and/or blinatumumab (n = 19), donor lymphocyte infusions (n = 29 pts), second allo-SCT (n = 37) and CAR T therapy (n = 14). The probability of overall survival (OS) at 1 and 5 years after relapse was 44% (95% confidence interval [CI]: 36%; 52%) and 19% (95% CI: 11%; 27%). In the 37 patients undergoing a second allo-SCT, the 5-year estimated OS probability was 40% [22%; 58%]. Younger age, recent allo-SCT, late relapse, 1st complete remission at 1st allo-SCT and chronic graft-versus-host disease confirmed their positive impact on survival in the multivariable analysis. CONCLUSION: Despite the poor prognosis of patients with ALL presenting relapse after a first allo-SCT, some can be satisfactorily rescued and a second allo-SCT still remains a valid option for selected patients. Moreover, emerging therapies really might improve ALL patients outcome when relapsing after an allo-SCT.

Fast surveillance response reveals the introduction of a new yellow fever virus sub-lineage in 2021, in Minas Gerais, Brazil.

BACKGROUND: In Brazil, the yellow fever virus (YFV) is maintained in a sylvatic cycle involving wild mosquitoes and non-human primates (NHPs). The virus is endemic to the Amazon region; however, waves of epidemic expansion reaching other Brazilian states sporadically occur, eventually causing spillovers to humans. OBJECTIVES: To report a surveillance effort that led to the first confirmation of YFV in NHPs in the state of Minas Gerais (MG), Southeast region, in 2021. METHODS: A surveillance network was created, encompassing the technology of smartphone applications and coordinated actions of several research institutions and health services to monitor and investigate NHP epizootics. FINDINGS: When alerts were spread through the network, samples from NHPs were collected and YFV infection confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and genome sequencing at an interval of only 10 days. Near-complete genomes were generated using the Nanopore MinION sequencer. Phylogenetic analysis indicated that viral genomes were related to the South American genotype I, clustering with a genome detected in the Amazon region (state of Pará) in 2017, named YFVPA/MG sub-lineage. Fast YFV confirmation potentialised vaccination campaigns. MAIN CONCLUSIONS: A new YFV introduction was detected in MG 6 years after the beginning of the major outbreak reported in the state (2015-2018). The YFV strain was not related to the sub-lineages previously reported in MG. No human cases have been reported, suggesting the importance of coordinated surveillance of NHPs using available technologies and supporting laboratories to ensure a quick response and implementation of contingency measures to avoid YFV spillover to humans.

Fast surveillance response reveals the introduction of a new yellow fever virus sub-lineage in 2021, in Minas Gerais, Brazil

BACKGROUND In Brazil, the yellow fever virus (YFV) is maintained in a sylvatic cycle involving wild mosquitoes and non-human primates (NHPs). The virus is endemic to the Amazon region; however, waves of epidemic expansion reaching other Brazilian states sporadically occur, eventually causing spillovers to humans. OBJECTIVES To report a surveillance effort that led to the first confirmation of YFV in NHPs in the state of Minas Gerais (MG), Southeast region, in 2021. METHODS A surveillance network was created, encompassing the technology of smartphone applications and coordinated actions of several research institutions and health services to monitor and investigate NHP epizootics. FINDINGS When alerts were spread through the network, samples from NHPs were collected and YFV infection confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and genome sequencing at an interval of only 10 days. Near-complete genomes were generated using the Nanopore MinION sequencer. Phylogenetic analysis indicated that viral genomes were related to the South American genotype I, clustering with a genome detected in the Amazon region (state of Pará) in 2017, named YFVPA/MG sub-lineage. Fast YFV confirmation potentialised vaccination campaigns. MAIN CONCLUSIONS A new YFV introduction was detected in MG 6 years after the beginning of the major outbreak reported in the state (2015-2018). The YFV strain was not related to the sub-lineages previously reported in MG. No human cases have been reported, suggesting the importance of coordinated surveillance of NHPs using available technologies and supporting laboratories to ensure a quick response and implementation of contingency measures to avoid YFV spillover to humans.

Impact of simultaneous placement of implant and block bone graft substitute: an in vivo peri-implant defect model.

BACKGROUND: Insufficient bone volume around an implant is a common obstacle when dental implant treatment is considered. Limited vertical or horizontal bone dimensions may lead to exposed implant threads following placement or a gap between the bone and implant. This is often addressed by bone augmentation procedures prior to or at the time of implant placement. This study evaluated bone healing when a synthetic TiO2 block scaffold was placed in circumferential peri-implant defects with buccal fenestrations. METHODS: The mandibular premolars were extracted and the alveolar bone left to heal for 4 weeks prior to implant placement in six minipigs. Two cylindrical defects were created in each hemi-mandible and were subsequent to implant placement allocated to treatment with either TiO2 scaffold or sham in a split mouth design. After 12 weeks of healing time, the samples were harvested. Microcomputed tomography (MicroCT) was used to investigate defect fill and integrity of the block scaffold. Distances from implant to bone in vertical and horizontal directions, percentage of bone to implant contact and defect fill were analysed by histology. RESULTS: MicroCT analysis demonstrated no differences between the groups for defect fill. Three of twelve scaffolds were partly fractured. At the buccal sites, histomorphometric analysis demonstrated higher bone fraction, higher percentage bone to implant contact and shorter distance from implant top to bone 0.5 mm lateral to implant surface in sham group as compared to the TiO2 group. CONCLUSIONS: This study demonstrated less bone formation with the use of TiO2 scaffold block in combination with implant placement in cylindrical defects with buccal bone fenestrations, as compared to sham sites.

[The last 50 years of pediatric cardiology (1971-2021): from Fontan operation to the present time]. / Cinquant'anni di cardiologia pediatrica (1971-2021): dall'intervento di Fontan ai nostri giorni.

Pediatric cardiology has matured profoundly over the last 50 years, paralleled by a similar development in pediatric cardiac surgery and cardiac anesthesia. This field of medicine provides structured and effective care for a very heterogeneous group of diseases including congenital heart disease, cardiomyopathies and heart failure, myocarditis, rheumatic heart disease, inherited and acquired arrhythmias, Kawasaki disease and more recently multisystemic inflammatory syndrome of children related to primary infection by SARS-CoV-2. This review summarizes achievements and results in selected topics of pediatric cardiology and cardiac surgery with focused attention to the diagnosis and management of congenital heart diseases.

Case Report: First Evidence of a Benign Bone Cyst in an Adult Teckel Dog Treated With Shark Teeth-Derived Bioapatites.

Bone cysts are a very rare orthopedic pathology in veterinary medicine, the general prevalence of which is unknown. A unicameral bone cyst was diagnosed in an adult female Teckel dog with a limp that was treated surgically by filling the defect with marine bioapatites. The treatment was effective and at 8 weeks the defect had remodeled 50.24%. Eighteen months after surgery, the defect had remodeled 94.23%. The limp disappeared after surgery, and functional recovery was good in all stages after surgery. No adverse reactions were observed at the local or systemic level. This is the first report of a benign bone cyst in an lame adult female Teckel successfully treated with a novel marine bioapatite.

Safety of anti-inflammatory drugs in children with asthma.

PURPOSE OF REVIEW: Inhaled corticosteroids (ICS) are widely used as the first-line treatment of asthma. When the disease is not controlled by standard doses of ICS, other anti-inflammatory drugs should be considered. The aim of this report is to review the main adverse events induced by anti-inflammatory drugs in children with asthma and discuss possible actions to prevent or mitigate these effects. RECENT FINDINGS: Proper interpretation of ICS safety studies requires knowledge of the pharmaceutical properties and delivery device systems of the different ICS available. Genetic variants affecting susceptibility to corticosteroid-induced adrenal suppression were found in children and adults who use ICS to treat their asthma. There is evidence of the association between montelukast use and neuropsychiatric events. SUMMARY: Benefits of ICS, properly prescribed and used, outweigh their potential adverse effects. There is substantial evidence that the combination of ICS with long-acting beta2 agonists is safe for asthmatic children. Awareness of the potential risks of neuropsychiatric events in children taking montelukast should inform the clinicians' prescribing practices. Omalizumab is generally well-tolerated, but the evidence on the safety of other biologic agents in children is scanty. The risk of systemic adverse events with anti-inflammatory drugs must be balanced against the risks of uncontrolled asthma and/or frequent oral steroid use.

Physiologic and Clinical Features of the Paralympic Athlete's Heart.

Importance: Paralympic medicine is a newly adopted term to describe the varied health care issues associated with athletes in the Paralympics. Scarce scientific data, however, are currently available describing the cardiac remodeling in Paralympic athletes. Objective: To investigate the physiological and clinical characteristics of the Paralympic athlete's heart and derive the normative values. Design, Setting, and Participants: This is a single-center study on a relatively large cohort of Paralympic athletes, conducted at the Italian Institute of Sport Medicine and Science. Paralympic athletes free of cardiac or systemic pathologic conditions other than their cause of disability were selected for participation in the Paralympic Games from January 2000 to June 2014. Athletes were arbitrarily classified for disability in 2 groups: those with spinal cord injuries (SCI) and those with non-SCI (NSCI). Data analysis occurred from March 2019 to June 2020. Main Outcomes and Measures: The primary outcome was the difference in cardiac remodeling in Paralympic athletes according to disability type and sports discipline type. Athletes underwent cardiac evaluation, including 12-lead and exercise electrocardiograms, echocardiography, and cardiopulmonary exercise testing. Results: Among 252 consecutive Paralympic athletes (median [interquartile range (IQR)] age, 34 [29-41] years; 188 men [74.6%]), 110 had SCI and 142 had NSCI. Those with SCI showed a higher prevalence of abnormal electrocardiogram findings than those with NSCI (13 of 110 [11.8%] vs 6 of 142 [4.2%]; P = .003), smaller left ventricular end-diastolic dimension (median [IQR], 48 [46-52] vs 51 [48-54] mm; P = .001) and left ventricular mass index (median [IQR], 80.6 [69-94] vs 91.3 [80-108] g/m2; P = .001), and lower peak oxygen uptake (VO2) (median [IQR], 27.1 [2-34] vs 38.5 [30-47] mL/min/kg; P = .001) in comparison with those with NSCI. Regarding sport discipline, endurance athletes had a larger left ventricular cavity (median [IQR], 52 [47-54] vs 49 [47-53] mm; P = .006) and higher peak VO2 (median [IQR], 46 [39-55] vs 30 [25-35] mL/min/kg; P = .001) than athletes in nonendurance sports. Conclusions and Relevance: Cardiac remodeling in Paralympic athletes differed by disability and sport discipline. Having NSCI lesions and engaging in endurance sports were associated with the largest left ventricular cavity and left ventricular mass and highest VO2 peak. Having SCI lesions and engaging in nonendurance disciplines, on the contrary, were associated with the smallest left ventricular cavity and mass and lowest VO2 peak.

Application of Shark Teeth-Derived Bioapatites as a Bone Substitute in Veterinary Orthopedics. Preliminary Clinical Trial in Dogs and Cats.

Background: The autograft is still considered the gold standard for the treatment of bone defects. However, given the significant morbidity of the donor site with which it has been associated, alternative substitutes for bone grafts have been developed. In the present study, a bone substitute composed of CaP biphasic bioceramics obtained from shark teeth was used (BIOFAST-VET). Objective: The objective of this study is to evaluate the efficacy of a marine bioapatite in the veterinary clinical field using it as a bone-grafting scaffold in dogs and cats. Methods: The biomaterial was randomly distributed in 6 veterinary clinical centers in Spain and was used in 24 cases (20 dogs and 4 cats) including 14 fractures, 9 arthrodesis, and 1 bone cyst. Grains between 500 and 2,000 µm were used. Inclusion and exclusion criteria were established. The time of consolidation and functional recovery were quantitatively and qualitatively assessed. For this, a follow-up was carried out at 2, 4, 8, and 12 weeks, included radiographic images, physical examination and sharing the feedback with the owners. Results: Nineteen cases completed the study (18 dogs and 1 cat; 11 fractures, 7 arthrodesis, and 1 bone cyst). The remaining five were excluded because they did not complete the radiographic follow-up (three cats and two dogs), being three arthrodesis and two fractures. In 18 of 19 cases, the use of the biomaterial was successful; the remaining one failed due to causes not related to the biomaterial. There were no systemic or local adverse reactions. Eighteen patients had a good functional recovery. The average consolidation time was 5.94 weeks in dogs with fractures and arthrodesis, not finding statistically significant differences between sex, weight, and procedure. Conclusions: This biomaterial is presented as a very suitable candidate for orthopedic surgery in the veterinary field. Preliminary results showed that its use reduces consolidation time in dogs with fractures and arthrodesis. In addition, no adverse systemic or local reactions have been observed derived from its use.

Coating doxycycline on titanium-based implants: Two in vivo studies.

Regardless of the substantial progress in designing titanium-based dental implants and aseptic techniques, infection remains as the most common complication after implantation surgeries. Although, having a weakened immune system or systematic diseases is not seen as contraindicated for dental implants anymore, controlling the immune system is required to avoid surgical site infections after implantation. These patients have to control the surgical site infections by taking a high daily dose of oral antibiotics after dental implantation. The antibiotics oral administration has many side effects such as gastrointestinal symptoms, skin rashes and thrush. Coating antibiotics on the biomaterials surface could be a promising solution to reduce these disadvantages through locally releasing antibiotics in a controlled manner. The aim of this study was to investigate the effects of doxycycline coating layer on titanium-zirconium alloy surfaces in vitro and in vivo. In our previous studies, we demonstrated the chemical presence of doxycycline layer in vitro. In this study, we examined its physical presence using field emission scanning electron microscope and confocal microscope. We also analyzed its controlled released manner using Nano-Drop UV Vis spectrometer. After in vitro characterization of the coating layer, we evaluated its effects on the implant osseointegration in dogs and rabbits. The histological and histomorphometrical results exhibited no significant difference between doxycycline coated and uncoated groups regarding the implants osseointegration and biocompatibility for dental applications. Therefore, coating a doxycycline layer on TiZr implants could be favorable for reducing or removing the antibiotics oral administration after the implantation surgery.

Pre-participation health evaluation in adolescent athletes competing at Youth Olympic Games: proposal for a tailored protocol.

OBJECTIVE: To promote sports participation in young people, the International Olympic Committee (IOC) introduced the Youth Olympic Games (YOG) in 2007. In 2009, the IOC Consensus Statement was published, which highlighted the value of periodic health evaluation in elite athletes. The objective of this study was to assess the efficacy of a comprehensive protocol for illness and injury detection, tailored for adolescent athletes participating in Summer or Winter YOG. METHODS: Between 2010 and 2014, a total of 247 unique adolescent elite Italian athletes (53% females), mean age 16±1,0 years, competing in 22 summer or 15 winter sport disciplines, were evaluated through a tailored pre-participation health evaluation protocol, at the Sports Medicine and Science Institute of the Italian Olympic Committee. RESULTS: In 30 of the 247 athletes (12%), the pre-participation evaluation led to the final diagnosis of pathological conditions warranting treatment and/or surveillance, including cardiovascular in 11 (4.5%), pulmonary in 11 (4.5%), endocrine in five (2.0%), infectious, neurological and psychiatric disorders in one each (0.4%). Based on National and International Guidelines and Recommendations, none of the athletes was considered at high risk for acute events and all were judged eligible to compete at the YOG. Athletes with abnormal conditions were required to undergo a periodic follow-up. CONCLUSIONS: The Youth Pre-Participation Health Evaluation proved to be effective in identifying a wide range of disorders, allowing prompt treatment, appropriate surveillance and avoidance of potential long-term consequences, in a significant proportion (12%) of adolescent Italian Olympic athletes.

Respiratory manifestations of gastro-oesophageal reflux in children.

Gastro-oesophageal reflux disease (GORD) is a complex problem in children. Suspected respiratory manifestations of GORD, such as asthma, chronic cough and laryngitis, are commonly encountered in the paediatric practice, but continue to be entities with more questions than answers. The accuracy of diagnostic tests (ie, pH or pH-impedance monitoring, laryngoscopy, endoscopy) for patients with suspected extraoesophageal manifestations of GORD is suboptimal and therefore whether there is a causal relationship between these conditions remains largely undetermined. An empiric trial of proton pump inhibitors can help individual children with undiagnosed respiratory symptoms and suspicion of GORD, but the response to therapy is unpredictable, and in any case what may be being observed is spontaneous improvement. Furthermore, the safety of these agents has been called into question. Poor response to antireflux therapy is an important trigger to search for non-gastro-oesophageal reflux causes for patients' symptoms. Evidence for the assessment of children with suspected extraoesophageal manifestations of GORD is scanty and longitudinal studies with long-term follow-up are urgently required.